T-4 Thyroid-stimulating hormone serum level, liver thyroid-stimulating hormone-receptor, and severe fibrosis in genotype 1 chronic hepatitis C patients with normal thyroid function

T-4 Thyroid-stimulating hormone serum level, liver thyroid-stimulating hormone-receptor, and severe fibrosis in genotype 1 chronic hepatitis C patients with normal thyroid function

Abstracts of the A.I.S.F. Annual Meeting 2012 / Digestive and Liver Disease 44S (2012), S1–S48 T-4 Thyroid-stimulating hormone serum level, liver thyr...

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Abstracts of the A.I.S.F. Annual Meeting 2012 / Digestive and Liver Disease 44S (2012), S1–S48 T-4 Thyroid-stimulating hormone serum level, liver thyroid-stimulating hormone-receptor, and severe fibrosis in genotype 1 chronic hepatitis C patients with normal thyroid function S. Petta 1 , A. Mazzola 1 , S. Grimaudo 1 , C. Cammà 1 , D. Cabibi 2 , V. Di Marco 1 , G.C. Morreale 1 , R.M. Pipitone 1 , A. Craxì 1 1 Cattedra 2 Cattedra

di Gastroenterologia, DiBiMIS, University of Palermo, Italy; di Anatomia Patologica, University of Palermo, Italy

Background/Aims: Hypo and hyperthyroidism have been associated with liver damage, and a recent study demonstrated a direct relation between thyroid-stimulating hormone serum levels and ALT levels also in a range of normal TSH values. In addition some evidences documented the presence of active TSH in the human liver. We aimed to assess if TSH serum levels, in a range of normality, and TSH receptor (TSHR) liver expression, are associated with the severity of fibrosis in patients with genotype 1 chronic hepatitis C (G1 CHC). Methods: 169 consecutive patients with G1 CHC, without known thyroid diseases and with normal TSH levels, were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by HOMA. TSH serum levels were measured by ELISA (MODULAR ANALYTICS E170, Roche). The liver mRNA expression of TSHR was tested by PCR in 53 patients. All biopsies were scored by one pathologist for staging and grading (Scheuer), and graded for steatosis. Results: Fifthy-one patients (30%) had fibrosis F3-F4, and mean TSH serum levels were 1.65±0.88 mU/L. By multivariate logistic regression analysis, necroinflammatory activity (OR 2,737; 95%CI 1,508-4,966; p=0.001), steatosis (OR 1,032; 95%CI 1,008-1,056; p=0.008), higher TSH levels (OR 1,994; 95%CI 1,218-3,265; p=0.006), and higher platelet levels (OR 1,003; 95%CI 1,001-1,005; p=0.001), were independently associated with severe fibrosis (≥F3). In addition patients with severe fibrosis had higher liver TSHR mRNA expression compared to those without severe fibrosis (n=19 vs 34; TSHR 0.610±0.442 vs 0.346±0.345, p=0.02). No association was found between serum TSH and liver mRNA TSHR (p=0.77). Conclusions: In G1CHC patients without thyroid diseases and with normal thyroid function, higher TSH serum levels and a higher hepatic expression of TSHR were associated with severe fibrosis, suggesting a profibrogenic role of TSH in the liver, by different mechanism.

T-5 High sCD36 plasma level is associated with steatosis and its severity in patients with chronic genotype 1 hepatitis C S. Petta 1 , A. Handberg 2 , G. Marchesini 3 , C. Cammà 1 , V. Di Marco 1 , D. Cabibi 4 , F.S. Macaluso 1 , A. Craxì 1 1 Sezione

di Gastroenterologia, DiBiMIS, Univ. of Palermo, Italy; 2 Dept. of Clinical Biochemistry, Aalborg Hospital, Aarhus Univ. Hospital, Aalborg, Denmark; 3 Dip. di Medicina Clinica, “Alma Mater Studiorum,” Univ. of Bologna, Italy; 4 Cattedra di Anatomia Patologica, Univ. of Palermo, Italy Background and Aims: Soluble CD36 (sCD36) plasma levels, a marker of cardiometabolic disorders, were associated with surrogate marker of steatosis, while experimental and human studies showed a link between CD36 expression in the liver and steatosis. In a cohort of patients with genotype 1 chronic hepatitis C (G1CHC), we tested the association of sCD36 plasma levels with host and viral factors and sustained virological response (SVR). Methods: One hundred seventy-five consecutive biopsy-proven G1CHC patients were studied. sCD36 plasma levels were assessed by an in-house ELISA. All biopsies were scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥20%. Patients underwent standard of care therapy with pegylated-interferon and ribavirin. Results: The severity of steatosis progressively increased according to sCD36 quartiles (p=0.02); total and LDL cholesterol levels were significantly higher in patients in the lower quartile compared to all the others. Gamma-glutamyl transferase (p=0.02), HOMA score (p=0.002), and sCD36 (p=0.04) were independently associated with the severity of steatosis as continuous variable.

S15

Multivariate logistic regression analysis showed that HOMA (OR 1.243, 95% CI 1.04-1.484, p=0.01) and sCD36 (OR 1.445, 95%CI 1.135–1.839, p= 0.003) were independently linked to steatosis ≥20%. No association was found between sCD36 and SVR. Conclusions: CD36 is linked to steatosis and insulin resistance in patients with G1CHC, but does not predict response to treatment. The potential of sCD36 as a surrogate marker of steatosis should be further investigated.

T-6 Hyperuricemia is associated with severe steatosis in patients with chronic hepatitis C S. Petta 1 , F.S. Macaluso 1 , D. Cabibi 2 , C. Cammà 1 , V. Di Marco 1 , A. Craxì 1 1 Sezione

di Gastroenterologia, DiBiMIS, University of Palermo, Italy; di Anatomia Patologica, University of Palermo, Italy

2 Cattedra

Background: Hyperuricemia have been associated with metabolic disorders. In this line recent studies observed an independent link between higher uric acid (UA) serum levels, and both clinical and histological diagnosis of nonalcoholic fatty liver disease (NAFLD), including its severity. Conversely, an association between Chronic Hepatitis C (CHC) and UA levels has been poorly investigated. Aims: We aimed to assess the potential association between UA serum levels and histological features of liver damage in a homogeneous cohort of biopsy-proven CHC patients. Methods: Consecutive CHC patients (n=496, HCV genotype 1 = 90.3%), assessed by liver biopsy (Scheuer score), anthropometric, biochemical and metabolic features, were included. Enzymatic colorimetric test was used for serum UA assays (Roche Diagnostics GmbH, Mannheim). Hyperuricemia was diagnosed when UA serum levels were >7 mg/dl in men, and >6 mg/dl in women. Results: Mean UA serum level was 4.7 mg/dl, whereas 7.5% of patients had hyperuricemia. This latter was independently associated with LDL cholesterol (OR 1.014, 95% CI 1.004–1.025, p=0.009), tryglicerides (OR 1.007, 95% CI 1.000–1.015, p=0.05), arterial hypertension (OR 2.753, CI 1.261–6.012, p=0.01) and eGFR (OR 0.956, 95% CI 0.937–0.976, p < 0.001) by multivariate logistic regression analysis. The following features were independently linked to severe steatosis (≥30%) by multiple logistic regression analysis: high BMI (OR 1.072, 95% CI 1.011–1.138, p=0.02), high tryglicerides (OR 1.005, 95% CI 1.000–1.011, p=0.04), and hyperuricemia (OR 2.930, 95% CI 1.273– 6.744, p=0.01). Higher UA levels were also associated with severe fibrosis (5.1±1.3 mg/dl in F3-F4 vs 4.7±1.2 mg/dl in F0-F2; p=0.008), even if at multivariate logistic regression analysis older age (OR 1.043, 95% CI 1.023– 1.064, p<0.001), low cholesterol (OR 0.990, 95% CI 0.984–0.997, p=0.004), high HOMA score (OR 1.100, 95% CI 1.007–1.201, p=0.03), moderate-severe grading (OR 2.934, 95% CI 1.858–4.634, p < 0.001) and severe steatosis (OR 2.224, 95% CI 1.278–3.869, p=0.005) remained significantly linked. Conclusions: In CHC patients, hyperuricemia was independently associated with severe steatosis, also indirectly affecting the severity of liver fibrosis. According to these data, in CHC UA could represent a novel potential therapeutic target in the disease management.

T-7 The course of bone mineral density in patients with chronic hepatitis B long term treated with nucleos(t)ide analogs: a longitudinal cohort study M. Viganò 1 , P. Lampertico 2 , R. Soffredini 2 , I. Chiodini 3 , F. Invernizzi 2 , F. Facchetti 2 , P. Beck-Peccoz 3 , M. Colombo 2 1 Hepatology Unit, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy; 2 1st Division of Gastroenterology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; 3 Endocrinology and Diabetology Unit, Department of Medical Sciences, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy

Background and Aim: Bone mineral density (BMD) may be impaired in patients with chronic hepatitis B (CHB) following long term administration of