Low Serum Levels of Zonulin in Patients with HCV-Infected Chronic Liver Diseases

Akao, Tomohiro; Morita, Ayumi; Onji, Morikazu; Miyake, Teruki; Watanabe, Ryouzi; Uehara, Takeki; Kawasaki, Keitarou; Miyaike, Jiro; Oomoto, Masaki

doi:10.5005/jp-journals-10018-1275

Cited by 6 publications

(4 citation statements)

References 12 publications

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“…The role of zonulin has also been previously investigated by others in small cohorts of patients with chronic liver disease. Serum zonulin levels were reported to decrease progressively, as liver function deteriorated in 9 patients with chronic viral hepatitis[ 18 ]. Obviously, such an under-powered study cannot lead to any valuable conclusion.…”

Section: Discussionmentioning

confidence: 99%

Serum zonulin levels in patients with liver cirrhosis: Prognostic implications

Voulgaris¹,

Karagiannakis²,

Hadziyannis³

et al. 2021

WJH

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BACKGROUND Increased gut permeability and bacterial translocation play an important role in liver cirrhosis. Zonulin is a recently recognized protein involved in the disintegration of the intestinal barrier. AIM To investigate possible differences in serum zonulin levels among patients with different cirrhosis stages and their potential prognostic implications. METHODS Consecutive cirrhotic patients who attended our liver clinic were included in the study. Serum zonulin levels, clinical, radiological and biochemical data were collected at baseline. Patients who accepted participation in a regular surveillance program were followed-up for at least 12 mo. RESULTS We enrolled 116 cirrhotics [mean Child-Turcotte-Pugh (CTP) score: 6.2 ± 1.6; model for end-stage liver disease score: 11 ± 3.9]. The causes of cirrhosis were viral hepatitis (39%), alcohol (30%), non-alcoholic fatty liver disease (17%), and other (14%). At baseline, 53% had decompensated cirrhosis, 48% had ascites, and 32% had history of hepatic encephalopathy. Mean zonulin levels were significantly higher in patients with CTP-B class than CTP-A class (4.2 ± 2.4 ng/dL vs 3.5 ± 0.9 ng/dL, P = 0.038), with than without ascites ( P = 0.006), and with than without history of encephalopathy ( P = 0.011). Baseline serum zonulin levels were independently associated with the probability of decompensation at 1 year ( P = 0.039), with an area under the receiving operating characteristic of 0.723 for predicting hepatic decompensation. Higher CTP score ( P = 0.021) and portal vein diameter ( P = 0.022) were independent predictors of mortality. CONCLUSION Serum zonulin levels are higher in patients with more advanced chronic liver disease and have significant prognostic value in identifying patients who will develop decompensation.

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Section: Discussionmentioning

confidence: 99%

Serum zonulin levels in patients with liver cirrhosis: Prognostic implications

Voulgaris¹,

Karagiannakis²,

Hadziyannis³

et al. 2021

WJH

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“…Increased proinflammatory cytokines are known to occur in other viral infections such as COVID-19 ( 43 ). In contrast to the NS1 administration, viral hepatitis B and C viral infections cause hepatocyte damage, leading to reduce zonulin synthesis ( 44 ). Therefore, our finding suggests that administration of NS1 results in the increase of proinflammation cytokines and acute phase proteins including zonulin.…”

Section: Discussionmentioning

confidence: 99%

The acute effects of nonstructural-1 protein dengue virus type 2 on wet liver weight, zonulin expression and serum zonulin

Jatmiko

Hartono

Ardyanto

et al. 2023

IJM

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Background and Objectives: Intestinal leakage commonly occurs in severe dengue infection with zonulin as a biomarker. The aim of this study was to determine the effects of NS1 on liver weight, zonulin expression and serum zonulin levels. Materials and Methods: This laboratory experiment used 18 ddY mice, which were randomly divided into control (C), PBS (T1), and PBS + NS1 (T2) groups. Mice in the T1 and T2 groups were intravenously injected with 500 µl PBS only and 50 µg NS1 respectively. Mice blood samples were collected before and after three-day treatment for measurement of zonulin level. The fresh liver was weighted directly and were then used for immunostaining. Results: The C group had lower wet liver weight compared to the T groups (p=0.001). Increased expression of liver zonu- lin was found in the T2 group, significant different from the C (p=0.014) and T1 groups (p=0.020). After treatment, serum zonulin levels in the T1 group was higher than that of the T1 group before treatment (p=0.035) but not in control (p=0.753) and T2 groups (p=0.869). Conclusion: Administration of 50 µg NS 1 increases wet liver weight and zonulin expression in hepatocytes, but did not increase serum zonulin levels in ddY mice.

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“…While in both severe liver injury (hepatitis) and cirrhotic patients, serum levels of ZFPs are significantly decreased as compared to controls. Akao and colleagues have described decreased ZFP levels both in patients with viral B and C hepatitis [3]. However, the authors did not measure levels of ZFPs in ascitic fluid.…”

Section: Discussionmentioning

confidence: 99%

Zonulin Family Peptide Levels in Ascites and Serum in Patients with Liver Cirrhosis: A Preliminary Study

et al. 2019

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Introduction Zonulin is a protein that reversibly modulates the permeability of tight junction of the small intestine wall. As the serum concentration of “zonulin family peptides” (ZFPs) is considered to be a sensitive and useful marker of intestinal wall permeability, its serum level may affect the volume of ascites fluid and change in gut microbiota. The aim of the study was to assess the association between concentrations of ZFPs in serum and ascites in relation to the severity of liver cirrhosis. Methods The preliminary study included 24 adult patients diagnosed with alcoholic or viral liver cirrhosis. 18 healthy adult subjects were enrolled as the control group. In patients and controls, there were measured serum and ascites (only in patients) ZFPs, serum bilirubin, creatinine, alanine aminotransferase, total protein, and C-reactive protein (CRP). Results Cirrhotic patients had lower serum hemoglobin (11.6 vs. 14.3 mg/dL; p < 0.001), platelet count (178 vs. 305 × 103/mm3; p < 0.01), total protein and albumin (58.6 vs. 74.3 g/dL; p < 0.001, 26.6 vs. 42.3 g/dL; p < 0.001, respectively), and serum ZFPs (30.5 vs. 62.0 ng/mL; p < 0.001) in comparison to controls. In patients with cirrhosis serum bilirubin, C-reactive protein level and INR were higher than in controls (3.07 vs. 0.96 mg/dL; 36.9 vs. 5 mg/L; 1.53 vs. 0.95; p < 0.001, respectively). Patients with low ZFP levels were characterized with lower ascites ZFP levels (0.25 vs. 16.4 ng/mL; p < 0.001) and ascites/serum index (0.011 vs. 0.462; p < 0.001). There were negative correlations between ascites ZFPs and platelet count (R = −0.497; p < 0.01) and positive correlation with INR (R = 0.640; p < 0.001). ZFP index positively correlated with platelet count (R = 0.726; p < 0.001) and negatively with INR (R = −0.392; p = 0.06). Conclusions Decrease serum ZFP levels seem to reflect their decreased liver synthesis but not increased gut permeability in patients with liver cirrhosis. The physiologically low level of ZFPs in transudate is increased in exudate.

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Low Serum Levels of Zonulin in Patients with HCV-Infected Chronic Liver Diseases

Cited by 6 publications

References 12 publications

Serum zonulin levels in patients with liver cirrhosis: Prognostic implications

Serum zonulin levels in patients with liver cirrhosis: Prognostic implications

The acute effects of nonstructural-1 protein dengue virus type 2 on wet liver weight, zonulin expression and serum zonulin

Zonulin Family Peptide Levels in Ascites and Serum in Patients with Liver Cirrhosis: A Preliminary Study

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