Increase in Serum MMP-9 and TIMP-1 Concentrations during Alcohol Intoxication in Adolescents-A Preliminary Study.

Background: Alcohol consumption by adolescents is responsible for a number of adverse health and social outcomes. Despite the well-established effect of alcohol use on the development of alcoholic liver disease, the relationship between the pattern of alcohol consumption and liver fibrosis is still unclear. This study is a follow-up to work on liver damage from alcohol intoxication. The aim of our study was to explore the early effects of alcohol intoxication on liver fibrosis in adolescents. Methods: The prospective study included 57 adolescents aged 14−17 years admitted to the emergency department (ED) from February 2017 to June 2018 due to acute alcohol intoxication. Serum levels of amino terminal propeptide of type III procollagen (PIIINP), type IV collagen, matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were determined by enzyme-linked immunosorbent assays. Results: There were significant differences in MMP-9 (p = 0.02) and TIMP-1 (p = 0.007) levels between the study and control groups. Liver parameters and selected markers of fibrosis were similar in groups in terms of blood alcohol concentrations (BAC). MMP-9 was positively correlated with alanine aminotransferase (ALT) (r = 0.38; p = 0.004) and total bilirubin (r = 0.39; p = 0.004). Positive significant correlations were also found between TIMP-1 and ALT (r = 0.47; p < 0.001), AST (r = 0.29; p = 0.03) and total bilirubin (r = 0.32; p = 0.02). In receiver operating characteristic (ROC) analysis, MMP-9 (AUC = 0.67, p = 0.02) and TIMP-1 (AUC = 0.69, p = 0.003) allowed for the differentiation of patients with and without alcohol intoxication. Conclusion: Our results show that even a single episode of alcohol intoxication in adolescents can lead to imbalance in markers of fibrosis.

Total Keratin-18 (M65) as a Potential, Early, Non-Invasive Biomarker of Hepatocyte Injury in Alcohol Intoxicated Adolescents-A Preliminary Study.

BACKGROUND: Underage drinking is associated with health risk behaviors. Serum keratin-18 (CK18) levels are increased in liver diseases and may be biomarkers of outcome. The purpose of this study was to determine if the total CK18 (M65) or caspase-cleaved CK18 (M30) levels were different in adolescents admitted to hospital because of alcohol intoxication and controls with excluded liver diseases. METHODS: A prospective study included 57 adolescents after alcohol use and 23 control subjects. The concentrations of M30 and M65 in the serum samples were evaluated using an enzyme-linked immunosorbent assay. RESULTS: The median age was 15 (14-17) years and 49% were male. There were significant differences in M65 levels between the study and control groups (p = 0.03). The concentrations of M30 and M65 were insignificant in adolescents divided into subgroups according to blood alcohol concentrations (BAC). Significant positive correlations were found between BAC and M65 levels (p = 0.038; r = 0.3). In receiver operating characteristic (ROC) analysis M65 (cut-off = 125.966 IU/l, Se = 70.2%, Sp = 43.5%) allowed to differentiate between patients with and without alcohol intoxication (AUC = 0.66, p = 0.03). CONCLUSION: M65 appears to be a promising non-invasive biomarker of hepatocyte injury during alcohol intoxication in adolescents. Moreover, a higher concentration of M65 may indicate early organ injury before the increase in the activity of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Liver pathology in children with newly diagnosed celiac disease.

AIM OF THE STUDY: To evaluate the prevalence and the type of liver pathology in children at the time of diagnosis of celiac disease (CD). MATERIAL AND METHODS: Data from newly diagnosed children with CD hospitalized in the university hospital were retrospectively reviewed. Liver pathology was defined as elevated alanine transaminase (ALT) and/or gamma-glutamyl transpeptidase (GGT) serum activity and/or pathological changes of the organ in ultrasound. RESULTS: Liver pathology was detected in 17 of 149 children (11.4%). Ten patients (6.7%) had an elevated ALT serum activity, whereas no child had an elevated GGT activity. Pathological changes of liver in ultrasound (mainly enlargement or steatosis of the organ) were found in 12 patients (8.1%), of whom 5 children (3.4%) had simultaneously elevated ALT serum activity. Children with liver pathology had lower iron (Fe) (p = 0.02) and folic acid (p = 0.01) concentrations compared to the rest of the patients. There were no statistically significant differences between liver pathology existence and age, sex, serum immunoglobulin A anti-tissue transglutaminase type 2 antibodies (IgA anti-TG2), ferritin, vitamin B12, or vitamin D concentrations. Moreover, a positive correlation between IgA anti-TG2 concentration and ALT serum activity was found (p < 0.01, R = 0.29). CONCLUSIONS: Liver pathology is present at diagnosis in a significant proportion of children with CD in the form of hypertransaminasemia and pathological changes of the organ in ultrasound. There is a correlation between IgA anti-TG2 concentration and ALT serum activity.

Chemerin as a novel non-invasive serum marker of intrahepatic lipid content in obese children.

BACKGROUND: Ectopic hepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of non-alcoholic fatty liver disease (NAFLD). The current study has shown that fat tissue constitutes an important endocrine organ with its own production and metabolism of many biologically active substances, among which adipokines play an important role. Classic adipokines (e.g. leptin, adiponectin, resistin) are fat-derived hormones which serum level is altered in patients with NAFLD. The role of novel adipokines in the pathomechanism of this disease is not clear. Therefore, the aim of our study was to evaluate the serum concentrations of chemerin, omentin and vaspin in obese children with NAFLD. METHODS: Forty-five obese children, aged 7-17 years old, were admitted to our Department with suspected liver disease (hepatomegaly, and/or ultrasonographic liver brightness, and/or increased ALT activity). Viral hepatitides, as well as autoimmune and metabolic liver diseases were excluded. Fasting serum levels of chemerin, omentin and vaspin were determined. The grade of liver steatosis in ultrasound was graded according to Saverymuttu. (1)HMR spectroscopy was performed with a 1.5 T scanner and with PRESS sequencing. RESULTS: Fatty liver was confirmed in 39 children by ultrasound and in 33 patients by (1)HMRS (19 of them also had increased ALT activity /NAFLD/). Chemerin and vaspin levels were significantly higher in children with NAFLD compared to the control group (n = 30). The concentration of chemerin was significantly higher in children with advanced liver steatosis compared to non-hepatopathic patients (p = 0,02). Significant positive correlations were found between the total liver lipids in (1)HMRS and chemerin (r = 0,33; p = 0,02) and vaspin (r = 0,4; p = 0,006). The ability of serum chemerin (cut-off = 190 ng/ml, Se = 75%, Sp = 58%) to differentiate children with fatty liver in (1)HMRS from those without steatosis was significant (AUC = 0,7, p = 0,04). Omentin and vaspin did not allow a useful prediction to be made. CONCLUSION: Chemerin seems to be the most suitable non-invasive biomarker in predicting both intrahepatic lipid content in obese children and advanced liver steatosis in children with NAFLD.

Cytokeratin-18 and hyaluronic acid levels predict liver fibrosis in children with non-alcoholic fatty liver disease.

OBJECTIVES: There is a need to replace liver biopsy with non-invasive markers that predict the degree of liver fibrosis in fatty liver disease related to obesity. Therefore, we studied four potential serum markers of liver fibrosis and compared them with histopathological findings in liver biopsy in children with non-alcoholic fatty liver disease (NAFLD). METHODS: We determined fasting serum level of hyaluronic acid (HA), laminin, YKL-40 and cytokeratin-18 M30 in 52 children (age range 4-19, mean 12 years, 80 % of them were overweight or obese) with biopsy-verified NAFLD. Viral hepatitis, autoimmune and metabolic liver diseases (Wilson's disease, alpha-1-antitrypsin deficiency, cystic fibrosis) were excluded. Fibrosis stage was assessed in a blinded fashion by one pathologist according to Kleiner. Receiver operating characteristics (ROC) analysis was used to calculate the power of the assays to detect liver fibrosis (AccuROC, Canada). RESULTS: Liver fibrosis was diagnosed in 19 children (37 %). The levels of HA and CK18M30 were significantly higher in children with fibrosis compared to children without fibrosis (p=0.04 and 0.05 respectively). The ability of serum HA (cut-off 19.1 ng/ml, Se=84 %, Sp=55 %, PPV=52 %, NPV=86 %) and CK18M30 (cut-off 210 u/l, Se=79 %, Sp=60 %, PPV=56 %, NPV=82 %) to differentiate children with fibrosis from those without fibrosis was significant (AUC=0.672 and 0.666, respectively). The combination of both markers was superior (AUC=0.73, p=0.002). Laminin and YKL-40 levels did not allow a useful prediction. CONCLUSIONS: Cytokeratin-18 and hyaluronic acid are suitable serum markers predicting liver fibrosis in children with NAFLD. Studying these markers may identify patients at risk of disease progression.

[The evaluation of hyaluronic acid and laminin concentration in serum in children with chronic hepatitis B treated with lamivudine, unresponsive to previous interferon-alpha therapy]. / Ocena stezenia kwasu hialuronowego i lamininy w surowicy dzieci chorych na przewlekle zapalenie watroby typu B leczonych lamiwudyna po nieskutecznej terapii interferonem alpha.

UNLABELLED: THE AIM OF THE STUDY was to evaluate prospectively serum hyaluronic acid (HA) and laminin (LAM) concentration in children with chronic hepatitis B (chB) during lamivudine treatment. MATERIAL AND METHODS: The observation was carried out on 40 children (29 boys and 11 girls), aged 4-17 yrs with biopsy proven chB who were nonresponders to previous IFN alpha therapy. Lamivudine was given in the dose of 3-4mg/kg/day up to 100 mg/day. The concentration of HA and LAM were measured with EIA technique in serum (CORGENIX and TAKARA kits respectively) before and after 12 months of therapy. RESULTS: After 12 months of therapy mean serum concentration of HA and LAM were lower then before treatment (20.3 +/- 13.3 vs 26.1 +/- 18.2 ng/ml, p=0.0112; 430 +/- 93 vs 455 +/- 161 ng/ml, p=NS respectively). The decrease of HA concentration was observed in subgroups of both responders and nonresponders (21.9 +/- 10.9 vs 26.1 +/- 10.6, p=NS; 20.1 +/- 13.7 vs 26.1 +/- 19.0, p=0.01 resp.). CONCLUSION: The decrease of HA and LAM serum concentration may suggest that lamivudine treatment inhibits liver fibrosis. Further studies with liver morphology evaluation are needed to confirm antifibrotic effect of lamivudine in children with chB.

Serum concentration of transforming growth factor (TGF)-beta 1 does not predict advanced liver fibrosis in children with chronic hepatitis B.

BACKGROUND/AIMS: The aim of the study was to evaluate if measurement of TGF-beta1 has clinical usefulness as a marker of liver fibrosis using ROC analysis and to assess its serum concentration during IFN alpha treatment. METHODOLOGY: Fibrosis stage and inflammation grade were assessed according to Batts and Ludwig and Ishak et al. before and 12 months after the end of IFN alpha treatment of 30 children with chronic hepatitis B. TGF-beta1 was measured by means of the quantitative sandwich enzyme immunoassay technique using recombinant human TGF-beta soluble receptor type II as a solid phase pre-coated onto a microplate (R&D System Inc., Minneapolis, USA). RESULTS: There was no significant correlation between serum TGF-beta1 level and the stage of liver fibrosis. However TGF-beta1 levels in patients before IFN alpha therapy were significantly higher than in controls. IFN alpha treatment did not improve histological fibrosis during 18 months of observation and it did not cause any significant changes in serum TGF-beta1 levels although there was a tendency to decrease its level during therapy and follow-up. CONCLUSIONS: Serum concentration of TGF-beta1 does not predict advanced liver fibrosis in children with chronic hepatitis B.

[The serum concentration of transforming growth factor beta1, interleukin 12 and interleukin 5 in children with chronic hepatitis B]. / Ocena stezenia transformujacego czynnika wzrostu beta 1, interleukiny 12 i interleukiny 5 w surowicy dzieci chorych na przewlekle zapalenie watroby typu B.

The aim of the study was to evaluate the serum TGF-beta 1, IL-12 and IL-5 concentration in children with chronic hepatitis (ChH) B. The study included 62 children with histopathologically diagnosed chh B. The stage of fibrosis and inflammation grade were assessed according to Batts and Ludwig and Ishak et al. The control group consisted of 9 children without clinical signs of infectious and chronic diseases. Serum TGF-beta 1 concentration was significantly elevated in patients with chronic hepatitis B (p = 0.0077) as compared to controls; there were no significant differences in serum concentrations of IL-12 and IL-5 between the examined groups of children. There was also no correlation between serum concentration of the studied cytokines and the degree of fibrosis, inflammation, activity of GPT, GOT, ALP, GGTP and concentrations of bilirubin, proteins or immunoglobulins (G, A, M).