Introduction

Although there is a childhood vaccination program against hepatitis B virus (HBV) in Greece, vaccination rates are thought to be suboptimal both in general population and in inflammatory bowel disease (IBD) patients^1,2. Wide use of new immunosuppressant and biologic therapy could lead to an oppurtunistic infection. As it is recommended by European Crohn's and Colitis Organisation (ECCO) for prevention of HBV infection, patients should be serologically screened at baseline, before and during an immunosuppressive therapy³ and be appropriately vaccinated. Vaccination is until now the most effective way in order to protect from HBV offering longtime protection. Lower successful immunization rates are seen after induction of immunosuppressant therapy carrying a higher risk of a current HBV infection and complications.There are limited epidemiological data about successful immunization, among Greek patients with inflammatory bowel disease, prior to immunosuppressant therapy initiation¹.

Aims & Methods

The aim was to detect the vaccination rate against HBV among IBD patients who are going to be treated with immunosuppressant therapy. Retrospectively collected data from medical records of IBD patients in a single referral IBD center between 2017 and 2023 were analyzed. Inclusion criteria were IBD patients prior to immunosuppressant therapy initiation with no natural immunity to HBV, absence of hepatitis B surface antigen (HBsAg), absence of isolated hepatitis B core antibody (anti-HBc) and any status of hepatitis B surface antibody (anti-HBs).

Results

In total 126 patients were included in the study with average age 46 years old (+/- 28 years old). 42.86% (54/126) of them were women and 57.14% (72/126) were men. 52.38% (66/126) had been diagnosed with Crohn's disease and 47.61% (60/126) with ulcerative colitis. In total 40,48% (51/126) had positive anti-HBs, because of successful immunization against HBV and 59.52% (75/126) were seronegative.

Conclusion

Our study confirms inadequate immunization results against hepatitis B among IBD patients in Greece. Intensive care should be given in vaccination protocols and serology testing especially in IBD patients that are going to start immunosuppressive agents. Primary care and IBD specialist should be well informed about serology testing and appropriate vaccination against hepatitis B, carefully advise and strongly recommend vaccination in IBD patients.

References

1. Fousekis FS, Katsanos KH, Theopistos VI, Baltayiannis G, Kosmidou M, Glantzounis G, Christou L, Tsianos EV, Christodoulou DK. Hepatobiliary and pancreatic manifestations in inflammatory bowel diseases: a referral center study. BMC Gastroenterol. 2019 Apr 3;19(1):48. doi: 10.1186/s12876-019-0967-3. PMID: 30943899; PMCID: PMC644630
2. Tsiligianni I, Bouloukaki I, Papazisis G, Paganas A, Chatzimanolis E, Kalatharas M, Platakis I, Tirodimos I, Dardavesis T, Tsimtsiou Z. Vaccination coverage and predictors of influenza, pneumococcal, herpes zoster, tetanus, measles, and hepatitis B vaccine uptake among adults in Greece. Public Health. 2023 Oct 9;224:195-202. doi: 10.1016/j.puhe.2023.09.002. Epub ahead of print. PMID: 37820537.
3. T Kucharzik, P Ellul, T Greuter, J F Rahier, B Verstockt, C Abreu, A Albuquerque, M Allocca, M Esteve, F A Farraye, H Gordon, K Karmiris, U Kopylov, J Kirchgesner, E MacMahon, F Magro, C Maaser, L de Ridder, C Taxonera, M Toruner, L Tremblay, M Scharl, N Viget, Y Zabana, S Vavricka, on behalf of the European Crohn’s and Colitis Organisation [ECCO], ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease, Journal of Crohn's and Colitis, Volume 15, Issue 6, June 2021, Pages 879–913

Clinical Case Summary

Clinical presentation: A 51-year-old male with a history of Crohn’s disease (CD) and liver transplantation due to primary sclerosing cholangitis under treatment with prednisolone, ustekinumab and tacrolimus presented with severe diarrhea. He reported a history of frequent hospitalizations due to salmonella and cambylobacter infections.
Investigations and differential diagnosis: Differential diagnosis included gastrointestinal infection or CD relapse. Blood and stool cultures were negative for bacteria or other organisms. Colonoscopy revealed deep ulcers and pseudopolyps on the right colon. Biopsies were obtained. On histology, lamina propria was expanded by sheets of PGM1-positive and CD1a-negative epithelioid macrophages engulfing round and targetoid laminated bodies. Their characterization as Michaelis–Gutmann bodies was confirmed by positive staining with PAS, Alcian Blue and von Kossa stains and negative for acid fast stains, thus rendering the diagnosis of malakoplakia. CMV co-infection was proven immunohistochemically by the detection of multiple CMV-positive histiocytes and endothelial cells (7 CMV-positive cells/high-power field).
Therapeutic approach: Intravenous ciprofloxacin, metronidazole and ganciclovir were administered while rapid prednisolone tapering was performed. His bowel movement gradually improved and he was discharged on day 10. Currently, he is in clinical remission under long-term ciprofloxacin treatment.
Discussion: Malakoplakia is related to inability of macrophages to digest phagocytosed gram-negative bacteria, resulting in accumulation of microorganism-laden histiocytes. Its pathophysiology relies on the severe derangement of immunity due to immunosuppression. The treatment is based on long-term antibiotic therapy. The awareness of such rare complications is mandatory in patients under immunosuppression and the usage of new biologic agents.

References

1. Endoscopic image from the right colon showing deep ulcers and pseudopolyps.
2. Histological image of Michaelis–Gutmann bodies (immunohistochemistry staining).

Introduction

Dominant stricture (DS) in Primary Sclerosing Cholangitis (PSC) is associated with a increased risk for Cholangiocarcinoma (CC)^1,2. The traditional definiton for DS (TDS) has been narrowing <1mm of common hepatic duct (CHD) and ducts <2cm within the bifurcation or <1,5mm of the common bile duct³. A new definition (NDS) has replaced TDS, including elevated cholestatic lab values (ALP, bil) and/or symptoms and response to treatment of the stricture (dilatation and/or stenting)⁴.

Aims & Methods

To compare clinical charasteristics of PSC patients and ocurance of biliary neoplasia with DS defined by either traditional (TDS) or new criteria (NDS).
In this longitudinal prospective cohort study, all patients who underwent Endoscopic Retrograde Cholangiography (ERC) for confirming of the diagnosis or screening for biliary dysplasia between October 2021 - 2022 were recruited. Laboratory values (P-ALP, P-Bil) and symptoms of cholestasis were collected before ERC. Bile duct disease severity was assesedby using Helsinki score⁵ and patients were classified as having no DS, TDS or NDS. Markers of biliary inflammation (IL-8, calprotectine) and biliary brush cytology were collected at time of ERC and laboratory values (P-ALP, P-Bil) 4 weeks after treatment of stricture. Ordinal variables were presented as median and interquartile range (IQR) and categorical variables as number and percentage. Fisher´s exact test, Chi-square test and Mann-Whitney tests were used when applicable.

Results

In total, 228 patients underwent 248 ERC:s: 28 (11%) to confirm the diagnosis and 216 (89%) for screening biliary dysplasia. TDS was detected in 62 (25%; 58 individual patients) and NDS in 43 (17%; 36 individual patients) ERC:s respectively; in the remaining 143 ERC:s no DS was seen. No differences were seen in disease duration (median 8 years), patient’s age or gender.
Not unexpectedly, patients with NDS had more symptoms (TDS 1, 2%; NDS 17, 40%; p < 0.001) and more frequently elevated cholestatic liver enzymes (TDS ALP med 94 U/l, IQR 74-129; NDS 288 U/l, IQR 233-419; p < 0.001).
Also, patients with NDS had more advanced bile duct disease based on Helsinki-score, see table.
Markers of biliary inflammation, biliary IL-8 and calprotectin were higher in NDS.
Patients with NDS needed more dilatation (81%) and stenting (21%) than those with TDS (60% and 5%, respectively).
No difference in amount of dysplasia were observed between NDS and TDS.

Conclusion

Patients with DS based on the new definition have significantly higher cholestatic lab values and are more often symptomatic. Patients with NDS present with more advanced bile duct disease and increased markers of biliary inflammation.

References

1. Rudolph G et al, J. Hepatol. 2010; 53(2):313-7.
2. Chapman MH, Eur J Gastroenterol Hepatol. 2012;24(9):1051-8.
3. Stiehl A et al. J Heptatol. 2002;36(2):151-156.
4. Ponsionen C. et al, Gastroenterology, 2021;161(6):1764-1775.
5. Boyd S. et al, Endoscopy 2016; 48(05): 432-439