Resolvin D1 (RvD1), a specialized pro-resolving lipid mediator, has been associated with liver injury in experimental models of alcohol-associated liver disease (ALD). This study aimed to evaluate the relationship between serum RvD1 levels and clinical phenotypes of ALD. This case-control study included 82 patients with ALD and 48 healthy controls (HCs). The ALD patients were categorized into three subgroups: alcohol-associated steatotic liver (ASL), alcohol-associated hepatitis (AH), and alcohol-associated cirrhosis (AC). Serum RvD1 levels were measured using the enzyme-linked immunosorbent assay (ELISA) test. The Fibrosis-4 (Fib-4) index was used to assess liver fibrosis in all participants. For the AH and AC groups, the Model for End-stage Liver Disease Sodium (MELD-Na) scores were calculated. Child-Pugh classification was applied to the AC patients and Maddrey’s Discriminant Function was applied to the AH patients. An esophagogastroduodenoscopy was performed in the AH and AC patients to evaluate portal hypertension. The serum RvD1 levels were significantly lower in the AH and AC groups compared to the ASL and HC groups (p < 0.001), with no significant difference between the AH and AC groups or between the ASL groups and the HC group. In the AC group, patients with ascites and/or esophageal/gastric varices had lower serum RvD1 levels compared to those without (p = 0.013 and p = 0.004, respectively). Additionally, the serum RvD1 levels decreased with advancing Child-Pugh class (p = 0.004). The serum RvD1 levels were inversely correlated with the Fib-4 scores, the MELD-Na and Child-Pugh scores in both the AC group (p < 0.05 for all). Serum RvD1 levels are associated with the severity of ALD and may represent a promising non-invasive biomarker. However, due to the absence of an external validation cohort, these findings should be interpreted as exploratory. Further validation in independent populations is warranted to confirm the clinical utility of RvD1 in ALD.

Introduction: Resolvin molecules have anti-inflammatory activity in inflammatory bowel diseases (IBDs). We aimed to evaluate whether serum resolvin D1 (RvD1) and resolvin E1 (RvE1) values can correlate to clinical and laboratory traits of IBDs. Methods: This case-control study included 62 patients with IBDs (32 ulcerative colitis (UC) patients, 30 Crohn’s disease (CD) patients) and 28 healthy controls. The Mayo Clinical scoring system (MCS) was used for the clinical and endoscopic features for UC, and the Crohn's disease activity index was used to assess the disease activity in CD patients. Human RvD1 and RvE1 kits were used for the serum enzyme-linked immunosorbent assay. Results: RvD1 concentrations were significantly lower in UC and CD patients compared to the control group [182.69 (118.24-450.80) ng/L and 342.07 (203.57-989.04) ng/L vs. 353.65 (216.14-1125.40) ng/L respectively, p=0.002]. RvD1 and RvE1 concentrations were higher in UC patients who were in the clinically remission phase than the patients in the activation phase [602.18 (176.13-1181.60) ng/L and 170.37 (113.21-216.21) ng/L, p=0.005 vs. 302.10 (122.18-527.37) ng/L and 74.17 (67.38-122.66) ng/L, p=0.004, respectively]. RvD1 values were higher in UC patients who had inactive endoscopic findings than the patients having active disease [426.11(175.94-891.03 ng/L and 169.62(109.97-202.80) ng/L, p=0.009, respectively]. The ROC (receiver operating characteristic curve) analysis revealed RvD1 and RvE1 levels had considerable diagnostic significances for the increased MCS in UC (AUC=0.809, 95%CI: 0.630-0.988, p<0.001 vs AUC=0.814, 95%CI: 0.637-0.991, p<0.001). Conclusion: Decreased serum RvD1 values might be used as an auxiliary biomarker for the diagnosis and the activity of UC.

Background/Aims: Histones are a part of neutrophil extracellular trap molecules which were reported to have diagnostic values in some inflammatory diseases. We aimed to evaluate whether serum histone H4 can be a diagnostic and prognostic marker for ulcerative colitis. Materials and Methods: This case–control study included 58 ulcerative colitis patients (34 males and 24 females) and 45 healthy controls (25 males and 20 females). The Mayo clinical scoring system was used for the clinical and endoscopic features. Truelove–Witt’s method was applied to the histology activity index. The human histone H4 kit was used for the enzyme-linked immunosorbent assay of serum histone H4. Results: Serum histone H4 was significantly lower in the ulcerative colitis group compared to the control groups [268 (14-1639) vs. 598 (310-2134) ng/L, P < .001, respectively]. Among the ulcerative colitis patients, there was no correlation between serum histone H4 and disease extent, Mayo clinical scoring, Mayo endoscopic activity subscoring, histology activity index, inflammatory markers, d-dimer, and leukocyte and neutrophil counts (r < 0.20, P > .05). Histone H4 levels were not statistically significant between the patients with no medication and those taking 5-aminosalicylate and/or other agents (P > .05). The receiver operating characteristic curve analysis revealed that serum histone H4 concentrations had a 0.782 (95%CI: 0.690-0.857, P < .001) diagnostic accuracy for ulcerative colitis. The specificity and sensitivity for the cutoff level of ≤364 ng/L were 88.9% and 72.4%, respectively. Conclusion: Decreased serum histone H4 values may be used as an auxiliary marker in the progression and diagnosis of ulcerative colitis. Further studies are needed to delineate this relationship between clinical and laboratory traits of ulcerative colitis and serum histone H4. Cite this article as: Küçük İ, Özçelik F, Yazgan Y, Yılmaz İ, Kaplan M, Yıldırım İ. Can serum histone H4 level be a biomarker in ulcerative colitis? Turk J Gastroenterol. 2024;35(1):4-10.

En tr Background: Many clinical activity indexes and non-invasive markers have been investigated for the evaluation of disease activity and regulation of treatment in ulcerative colitis (UC), but none have been as accurate as histopathological and endoscopic examinations in detecting inflammatory activity. We aimed to examine the relationship between the simple and easily achievable neutrophil/lymphocytes-platelet (N/LP) ratio in clinical disease activity in UC and the endoscopic severity of the disease. Methods: According to the results of the Baron score and Clinical Colitis Activity Index (CCAI), 32 patients with active, 37 patients with remission total of 69 UK patients and 36 healthy participants were included in the study. Absolute neutrophil count, neutrophil/lymphocyte ratio (NLR), N/LP, mean platelet volume (MPV), C-reactive protein and erythrocyte sedimentation rate were measured and recorded. Results: A significant increase in NLR was observed in the active UC group and the inactive UC group compared to the controls (2.98±1.69, 2.56±1.2, 1.59±0.43 respectively, p<0.0001). However, although there was a difference between the active UC group and the remission group, it was not statistically significant (p =0.284). A significant increase in N/LP was observed in the active UC group and the inactive UC group compared to the controls (0.96±0.4, 0.9±0.4, 0.7±0.2; p<0.0001, respectively). However, although there was a difference between the active UC group and the remission group, it was not statistically significant (p=0.588). Sedim and CRP were found to be significant independent markers to differentiate disease activity (p<0.05 and p<0.05, respectively). Discussion: NLRs and N/LPs showed a significant difference in ulcerative colitis patients compared to the control group. However, these parameters were assessed that ulcerative colitis patients cannot be used as a biomarker to detect the activation-remission difference. Amaç: Ülseratif kolitte (ÜK) hastalık aktivitesinin değerlendirilmesi ve tedavinin şekillendirilmesi için birçok klinik aktivite indeksi ve non invaziv belirteç araştırılmış fakat hiçbiri inflamatuvar aktivitenin saptanmasında histopatolojik ve endoskopik incelemeler kadar kesin bulgu vermemiştir. Basit ve kolayca elde edilebilen nötrofillerin lenfosit ve plateletlere (N/LP) oranının ÜK'deki klinik hastalık aktivitesi ve hastalığın endoskopik şiddeti arasındaki ilişkiyi incelemeyi amaçladık. Yöntemler: Baron skoru ve Klinik Kolit Aktivite İndeksi (CCAİ) bulgularına göre 32 si aktif, 37 si remisyonda toplam 69 ÜK hastası ve 36 sağlıklı katılımcı çalışmaya dahil edildi. Mutlak nötrofil sayısı, NLR, N/LP, MPV, C-reaktif protein ve Eritrosit sedimantasyon hızı ölçüldü ve kaydedildi. Sonuçlar: Aktif ÜK grubunda ve aktif olmayan ÜK grubunda kontrollere kıyasla önemli derecede nötrofil/lenfosit oranında (NLR) yükselme gözlendi (sırasıyla 2,98±1,69, 2,56±1,2, 1,59±0,43; p<0,0001). Fakat aktif ÜK grubu ile remisyon grubu arasında fark olmasına rağmen istatistiksel olarak anlamlı değildi (p<0,284). Aktif ÜK grubunda ve aktif olmayan ÜK grubunda kontrollere kıyasla önemli derecede N/LP yükselmesi gözlendi (sırasıyla 0,96±0,4, 0,9±0,4, 0,7±0,2; p<00001). Fakat aktif ÜK grubu ile remisyon grubu arasında fark olmasına rağmen istatistiksel olarak anlımlı değildi(p=0,588). Sedim ve CRP'nin hastalık aktivitesini ayırt etmek için anlamlı bağımsız belirteçler olduğu bulundu (sırasıyla p<0,05, p<0,05). Tartışma: NLR'ler ve N/LP'ler, kontrol grubuna kıyasla ülseratif kolit hastalarında anlamlı farklılık göstermiştir. Fakat bu parametreler ülseratif kolit hastalarının aktivasyon-remisyon farkını saptamada bir biyobelirteçleri olarak kullanılamayacağı değerlendirilmiştir.

Aim: Inflammatory indexes can relate to disease activity in ulcerative colitis (UC). This study aimed to evaluate whether the inflammatory indexes of neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP)-albumin ratio (CAR), CRP-lymphocyte ratio (CLR), and systemic immune-inflammation index (SIII) might predict the severity of mucosal inflammation in UC. Material and Methods: This retrospective case-control study included 184 UC patients and 101 healthy controls. The Mayo clinical score and Mayo endoscopic score were used for the clinical and endoscopic features of UC. Truelove and Richards’s method for the severity of mucosal inflammation determined the histological activity index (HAI). Results: The inflammatory index values, were higher in UC patients compared to the control group (p=0.007 for NLR, and p<0.001 for the others). The patients having endoscopic, clinic, and histologically active disease had higher inflammatory index values than those in remission (p<0.001 for all). UC patients with extensive disease had higher inflammatory index values than the patients who had limited disease (p<0.001 for all). The HAI values were positively correlated to all inflammatory indexes, and the correlation was the strongest between the HAI and CLR (rho=0.737, p<0.001). Regarding HAI, the diagnostic accuracy of all inflammatory indexes for detecting the clinically active disease was statistically significant, and there was no significant difference between them in terms of diagnostic accuracy. Conclusion: The inflammatory indexes of NLR, CAR, CLR, and SII might predict the severity of histological inflammation in UC.