Psoriasis and the liver: problems, causes and course.

BACKGROUND/OBJECTIVES: Psoriasis patients have a higher risk of liver abnormalities such as non-alcoholic fatty liver disease (NAFLD), drug-induced hepatitis, alcoholic hepatitis and neutrophilic cholangitis, than the general population. Associated liver disease limits therapeutic options and necessitates careful monitoring. The aim of the study was to identify liver problems in psoriasis patients and to investigate the underlying causes as well as their course. METHODS: The files of 518 psoriasis patients were retrospectively reviewed. Among these, 393 patients with relevant laboratory data were analysed for liver enzymes and their relation to the known risk factors for liver disease (obesity, diabetes mellitus, alcohol consumption, hepatotoxic medications, dyslipidemia, psoriatic arthritis and infectious hepatitis). RESULTS: Among 393 patients, 24% and 0.8% developed liver enzyme abnormalities and cirrhosis, respectively. The most common factors associated with pathological liver enzymes were drugs (57%) and NAFLD (22%). Other rare causes were alcoholic hepatitis, viral hepatitis, neutrophilic cholangitis, autoimmune hepatitis and toxic hepatitis due to herbal therapy. Drug-induced liver enzyme abnormalities were reversible whereas in patients with NAFLD transaminases tended to fluctuate. One patient with herbal medicine-related cirrhosis died of sepsis. CONCLUSION: Liver enzyme abnormalities are common in psoriasis patients and are mostly associated with drugs and NAFLD. Although most cases can be managed by avoiding hepatotoxic medications and close follow up, severe consequences like cirrhosis may develop.

Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease.

OBJECTIVE: The novel adipokines omentin, chemerin, and adipsin are associated with insulin resistance and the components of the metabolic syndrome. We assayed circulating levels of these molecules and examined their association with clinical, biochemical, and histological phenotypes in patients with nonalcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: Serum levels of omentin, chemerin, and adipsin were assayed by enzyme-linked immunosorbent assay in 99 patients with biopsy-proven NAFLD and 75 control subjects. We analyzed associations between adipokines and the characteristics of patients with NAFLD using multivariable linear regression models. RESULTS: Adipsin levels did not differ between patients and controls, whereas both omentin and chemerin levels were significantly higher in patients with biopsy-proven NAFLD than in controls (both p values <0.001). Serum omentin levels were significantly associated with C-reactive protein (r = 0.29, p < 0.01) and the degree of hepatocyte ballooning (r = 0.27, p < 0.01), whereas chemerin showed a modest association with liver fibrosis (r = 0.22, p = 0.04). After stepwise linear regression analysis adjusting for potential confounders, serum omentin levels retained their independent significance as a predictor of hepatocyte ballooning in patients with NAFLD (ß = 1.42; t = 2.79, p < 0.01). CONCLUSIONS: Our results suggest that serum omentin levels are raised in patients with NAFLD regardless of potential confounders and represent an independent predictor of hepatocyte ballooning.

Serum zinc-α2-glycoprotein concentrations in patients with non-alcoholic fatty liver disease.

BACKGROUND: Evidence suggests that zinc-α(2)-glycoprotein (ZAG) might serve as a biomarker for human metabolic alterations. We measured serum ZAG in patients with non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, and examined its association with clinical, biochemical, and histological phenotypes. METHODS: Serum ZAG was determined using ELISA in 90 patients with biopsy-proven NAFLD and 81 controls. RESULTS: Serum ZAG concentrations did not differ in patients with NAFLD (median 61 µg/mL; interquartile range: 56-73 µg/mL) compared with healthy controls (median 66 µg/mL; interquartile range: 56-78 µg/mL, Mann-Whitney U-test, p=NS). However, among patients with NAFLD serum ZAG concentrations were significantly higher in males and in those with the metabolic syndrome. After stepwise linear regression analysis, serum ZAG concentrations were the only independent predictor of the number of metabolic syndrome components in patients with NAFLD (ß=0.22; t=2.001, p<0.05). CONCLUSIONS: In summary, the hypothesis of an association between NAFLD and serum ZAG concentrations is not supported by the present results. However, ZAG remains an interesting molecule for further research in the field of human metabolic disorders.

Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease.

BACKGROUND: The fibroblast growth factor 21 (FGF21) hormonal pathway is a metabolic signalling cascade and has been recently identified as the master hormonal regulator of glucose, lipids and overall energy balance. In this observational, case-control study, we assayed serum levels of FGF21 in patients with nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, and examined their association with clinical, biochemical and histological phenotypes. MATERIALS AND METHODS: Serum levels of FGF21 were assayed by ELISA in 82 patients with biopsy-proven NAFLD and 77 controls. We analysed associations between FGF21 and the characteristics of patients with NAFLD by multiple linear regression analysis. RESULTS: Levels of FGF21 were significantly higher in patients with NAFLD (median 200 pg mL(-1) ; interquartile range: 87-410 pg mL(-1)) than in healthy controls (median 93 pg mL(-1) ; interquartile range: 70-180 pg mL(-1) , Mann-Whitney U-test, P<0·001). There was a stepwise increase in serum FGF21 levels according to the liver steatosis score (median level in subjects with score 1: 170 pg mL(-1) ; score 2: 220 pg mL(-1) ; score 3: 280 pg mL(-1) , P for trend <0·01). After stepwise linear regression analysis, serum FGF21 levels were the only independent predictor of hepatic steatosis scores in patients with NAFLD (ß=0·26; t=2·659, P<0·01). CONCLUSIONS: Serum FGF21 levels are increased in patients with NAFLD regardless of potential confounders and represent an independent predictor of liver steatosis. These findings support further investigation of this molecule in metabolic liver diseases.

Serum levels of osteoprotegerin in the spectrum of nonalcoholic fatty liver disease.

OBJECTIVE: Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily with pleiotropic effects on inflammation, endocrine function and the immune system. Reduced OPG levels are related to insulin resistance. We tested the hypothesis that serum levels of OPG may be associated with nonalcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: Four groups of patients were enrolled in the present study: subjects with definite nonalcoholic steatohepatitis (NASH, n = 56), borderline NASH (n = 26), simple fatty liver (n = 17) and healthy controls without evidence of liver disease (n = 58). Serum levels of OPG were measured by ELISA. RESULTS: Concentrations of OPG were significantly lower in patients with definite NASH (median: 45 pg/mL, p < 0.001) and borderline NASH (57 pg/mL, p < 0.001) than in controls (92 pg/mL). The area under the ROC curve for distinguishing between steatohepatitis (definite NASH plus borderline NASH) and healthy controls using OPG was 0.82. The use of a cut-off level < 74 pg/mL for serum OPG levels yielded sensitivity and specificity values of 75.6% and 75.9%, respectively. CONCLUSIONS: Serum osteoprotegerin concentrations are reduced in patients with the more severe forms of NAFLD and may serve as a noninvasive biomarker to identify patients with NASH.

Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats.

Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti-inflammatory and anti-apoptotic agent. We aimed to evaluate the effects of melatonin on methionine- and choline-deficient diet (MCDD)-induced NASH in rats. Thirty-two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair-fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.'s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti-inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.

The effects of pegylated interferon alpha 2b on bile-duct ligation induced liver fibrosis in rats.

OBJECTIVE: To test the effects of peginterferon in an unrecoverable model of bile-duct ligation (BDL) induced liver fibrosis. MATERIAL AND METHODS: Thirty-seven Wistar rats were divided into five groups: group 1, BDL + peginterferon (n = 8); group 2, BDL (n = 8); group 3, sham + peginterferon (n = 7); group 4, sham (n = 7); and group 5, control group (n = 7). Peginterferon-alpha 2b (50 microgr/kg) or saline (1 mL/kg) was administered intraperitonealy every week for four weeks. Serum biochemical markers, liver tissue oxidative stress, collagen and transforming growth factor-beta (TGF-beta) levels were examined after four weeks. Liver slides were stained by hematoxylin and eosin and Masson trichrome\Gomory reticulum staining. RESULTS: The levels of tissue collagen, TGF-beta, biochemical markers (AST, ALT, bilirubins, alkaline phosphates, gamma-glutamyl transpeptidase) and oxidative stress markers (Malondialdehyde, luminal, lucigenin) of the BDL group were higher than the sham operated and control groups (all-p < 0.001). Peginterferon improved malondialdehyde, luminal and glutathione levels in the BDL + peginterferon group (p < 0.05). Histopathological examination of the BDL groups showed stage-3 fibrosis, while all the control groups were normal. Peginterferon showed no improvement in fibrosis either histologically, or biochemically. CONCLUSIONS: Peginterferon improved levels of malondialdehyde, glutathione and luminal in the rat model of BDL induced liver fibrosis. Peginterferon however,showed no anti-fibrotic effects in this model and therefore may not be a useful treatment for liver fibrosis.

Is HCV genotyping cost-effective even when the prevalences of genotypes 2 and 3 are low?

BACKGROUND/AIMS: The management of chronic hepatitis C virus (HCV) infection is costly. Genotyping determines the indication, probability of response, and duration of treatment and the dose of ribavirin. Although genotyping is accepted cost-effective, the cost of genotyping in all of the patients to find out a minority may offset the gain. The present study aimed; (1) to determine the frequency rate of HCV genotypes and (2) to compare the cost of HCV treatment tailored according to the genotype versus that planned supposing it to be genotype 1. METHODOLOGY: Six centers were included into the study. Name, age, genotype, and serotype of each patient were entered. For genotyping, HCV-RNA was extracted by acid-guanidium-phenol-chloroform method. Cost of genotyping, HCV-RNA studies and the treatment with pegylated interferon and ribavirin was estimated. The cost was determined according to two scenarios: (A) To manage patients as if all had genotypes other than 2-3. (B) To manage them after determining the geno type. The management was assumed to be made by current guidelines. RESULTS: The data of 834 patients were analyzed: Genotypel was predominant: 730 (87.5%). The rest was composed of G2:26 (3.1%), G3:26 (3.1%), G4:14 (1.7%), mixed: 13 (1.6%), undetermined: 25(3%). The cost of approach A (for 100 patients) was 1,718,200 USD; that of approach B (for 100 patients) was 1,671,900 USD. With genotype targeted therapy, every 100 patient would save 46,300 USD. CONCLUSIONS: The prevalent genotype in our country is genotypel. The sum of genotypes 2 and 3 corresponds to 6%. Genotyping HCV and tailoring the treatment thereafter are cost-effective even in the countries where prevalence of these genotypes is low.

Tumor necrosis factor-alpha inhibitors for the treatment of psoriasis patients with liver cirrhosis: A report of four cases with a literature review.

Patients with psoriasis are at an increased risk of developing liver disease due to various factors. The existing data regarding the treatment of psoriasis patients with associated liver cirrhosis is limited. We report four patients of psoriasis with liver cirrhosis who were treated with TNF-alpha inhibitors for a mean duration of 35.4 months. Two patients were treated with etanercept, one with adalimumab and one was treated with both infliximab and etanercept. Three patients tolerated the treatment well without any deterioration of liver disease whereas one died of progressive liver disease. Although large-scale, controlled studies are needed, this case series provides insights regarding the long-term safety of TNF-alpha inhibitors in patients with psoriasis and liver cirrhosis.

Prothrombotic gene mutations and Crohn's disease; is there any association?

BACKGROUND/AIMS: Patients with inflammatory bowel disease have an increased tendency for thromboembolism. In this study we aimed to determine the frequency of FV gene and Prothrombin G20210A gene mutations in a group of patients with Crohn's Disease (CD) and estimate its correlation with disease activity and clinical subtype. METHODOLOGY: Forty-four CD patients and 43 healthy controls were included in the study. Twenty-three of the patients had inflammatory CD, while 11 had fibrostenotic and 10 had fistulizing CD. Only one patient had a history of deep vein thrombosis. Polymorphism Light Cycler FV Leiden mutation detection kit and Light Cycler prothrombin (G20210A) mutation detection kit were used for the detection of mutations in DNA samples. RESULTS: Forty of the CD patients had normal factor V genotype, three (6.8%) patients showed a heterozygous, and one (2.3%) patient homozygous pattern. Two (4.7%) of the 43 controls showed heterozygous factor V mutation and 41 had normal FV genotype. Two (4.6%) CD patients had heterozygous prothrombin G20210A mutation, and there was only one (2.3%) homozygous mutation in the control group. There was no significant difference between controls and CD patients neither for factor V mutation (p > 0.05) nor for prothrombin G20210A mutations (p > 0.05). No correlation was found between disease activity and both gene mutations (p > 0.05), as well as between disease subtype and gene mutations (p > 0.05). CONCLUSIONS: The prevalence of prothrombin G20210A gene and factor V Leiden gene mutations were found to be statistically insignificant among CD patients and control group.

Determination of hepatitis B genotypes in patients with chronic hepatitis B virus infection in Turkey.

BACKGROUND/AIMS: There are significant variations in the geographic distribution of hepatitis B virus genotypes throughout the world, and some genotypes are associated with different clinical outcomes. Eight genotypes of human hepatitis B virus (designated A-H) have been described to date. To determine the hepatitis B virus genotypes in Turkish patients with chronic liver disease and compare the results with clinical characteristics of the patients. METHODS: Fifty-four (pediatric: n=25 and adult: n=29) patients with chronic hepatitis B virus infection and with an hepatitis B virus DNA level above 5 pg/ml were entered into the trial. Restriction fragment length polymorphism method was used to determine hepatitis B virus genotype and their restriction fragment length polymorphism patterns. Hepatitis B virus DNA samples of 13 patients were sequenced automatically for further confirmation of restriction fragment length polymorphism results. RESULTS: Genotype D was the dominant genotype in all of our cases. Among six restriction fragment length polymorphism patterns of genotype D reported in the literature, three (D1, D2, D6) were present in our series and D2 was the most frequent restriction fragment length polymorphism pattern (81.5%). No significant differences were observed among different genotype D restriction fragment length polymorphism patterns with respect to patients' serum ALT, AST, and hepatitis B virus DNA titer, but D2 restriction fragment length polymorphism pattern was significantly more common in younger adults compared to D1 restriction fragment length polymorphism pattern. CONCLUSION: Genotype D with D2 restriction fragment length polymorphism pattern is the dominant hepatitis B virus genotype in all age groups in Turkey.

Effects of selective COX-2 inhibitors on the gastric permeability of sucrose: a controlled study with placebo and ibuprofen.

OBJECTIVE: Acute and chronic use of non-steroidal anti-inflammatory drugs can increase gastrointestinal permeability. Celecoxib, which selectively inhibits the enzyme cyclooxygenase-2, is a novel anti-inflammatory drug with minimal gastrointestinal toxic effects while retaining anti-inflammatory efficacy. Our aim was to assess the potential effects of celecoxib on gastric permeability in comparison with placebo and ibuprofen. DESIGN: We conducted a prospective, double-blind, cross-over study. SETTING: This study is carried out at Marmara University Hospital. PARTICIPANTS: Twenty-five healthy subjects entered the study but 19 subjects completed the treatment. INTERVENTION: Subjects were randomized to celecoxib 100 mg twice daily, ibuprofen 600 mg twice daily or placebo for 7 days in pre-defined sequences. Treatments were separated by a 7 day washout period. MAIN OUTCOME MEASURE: Gastric permeability was assessed by measuring urinary excretion of sucrose spectrophotometrically. RESULTS: Ibuprofen 600 mg twice daily produced greater increases in gastric permeability compared with placebo or celecoxib (geometric mean of urinary sucrose recovery was 59.15, 32.65 and 33.11 mg/h for ibuprofen, placebo and celecoxib, respectively) (P < 0.001). Celecoxib was generally better tolerated than ibuprofen. CONCLUSIONS: When compared with ibuprofen, celecoxib 100 mg twice daily has no significant effect on gastric mucosa in healthy subjects.

Gastric polypoid lesions: analysis of 150 endoscopic polypectomy specimens from 91 patients.

AIM: To analyze gastric polypoid lesions in our patient-population with respect to histopathologic features and demographic, clinical, and endoscopic characteristics of patients. METHODS: Clinical records and histopathologic reports of patients with gastric polypoid lesions were analyzed retrospectively. All lesions had been totally removed by either endoscopic polypectomy or hot biopsy forceps. The histopathologic slides were re-evaluated by the same histopathologist. RESULTS: One-hundred and fifty gastric polypoid lesions were identified in 91 patients. There were 53 (58%) women and 38 (42%) men with a median age of 53 (range, 31 to 82) years. The most frequent presenting symptom was dyspepsia that was observed in 35 (38.5%) patients. Symptoms were mostly related to various associated gastric abnormalities such as chronic gastritis or H pylori infection rather than polypoid lesion itself. Polypoid lesions were commonly located in the antrum followed by cardia. Out of 150 lesions, 80 (53%) had the largest dimensions less than or equal to 5 mm and only 7 were pedunculated. The frequencies of hyperplastic polyps, foveolar hyperplasia, and fundic gland polyps were 46%, 18%, and 14% respectively. We also detected gastritis varioliformis in 12 specimens, lymphoid follicles in 9, 4 adenomatous polyps in 4, polypoid lesions with edematous mucosa in 4, inflammatory polyps in 3, and carcinoid tumor in 1. Adenomatous changes were observed within two hyperplastic polyps and low grade dysplasia in one adenoma. Histopathologic evaluation of the surrounding gastric mucosa demonstrated chronic gastritis in 72 (79%) patients and H pylori infection in 45 (49%). CONCLUSION: Hyperplastic polyps are the most frequently encountered subtype of gastric polypoid lesions. They are usually associated with chronic gastritis or H pylori gastritis. Contrary to the previous belief, they may harbour adenomatous changes or dysplastic foci. Therefore, endoscopic polypectomy seems as a safe and fast procedure for both diagnosis and treatment of gastric polypoid lesions at the same session. In addition, edematous mucosa may appear misleadingly as a polypoid lesion in some instances and it can be ruled out only by histopathologic examination.

The utility of cytokeratins 7 and 20 (CK7/20) immunohistochemistry in the distinction of short-segment Barrett esophagus from gastric intestinal metaplasia: Is it reliable?

BACKGROUND: The purpose of the present correlative immunohistochemical study was to assess the utility of cytokeratin (CK7 and CK20) expression in the diagnosis of short-segment Barrett esophagus, particularly its efficacy in differentiating Barrett mucosa from intestinal metaplasia of the gastric cardia and corpus. METHODS: Two groups of endoscopic biopsy specimens were examined, including 20 endoscopic biopsy specimens of short-segment Barrett esophagus (Group A) and equal number exhibiting Helicobacter pylori associated intestinal metaplasia of the gastric cardia and corpus (Group B). All were investigated by immunohistochemistry using the standard ABC method for CK7 and CK20 expression. Fisher's exact test was used for statistical analysis of Barrett CK7/20 and gastric CK7/20 patterns between the groups. RESULTS: The anticipated pattern of reactivity in Barrett mucosa (CK7: strong diffuse positivity in superficial and deep glands; CK20: positivity in surface epithelium and superficial glands) was seen in 2 cases of Group A specimens. The expected gastric pattern (CK7: patchy immunostaining with variable involvement of deep glands; CK20: patchy immunostaining of superficial and deep glands in incomplete intestinal metaplasia / absence of CK7 immunoreactivity with strong CK20 staining in superficial and deep glands in complete intestinal metaplasia) was seen in 8 cases of Group B specimens. The respective sensitivity and false-negativity values of CK7/20 staining for Barrett pattern in Group A were 10% and 90%, respectively. These values for gastric pattern in Group B were 40% and 60%, respectively. The specificity and false-positivity values of both patterns were same (100% and 0%, respectively). There was no statistically significant difference for Barrett pattern between the two groups (P = 0.487), while the observation of gastric pattern was significantly higher in Group B than in Group A (P = 0.02). CONCLUSIONS: We concluded that these hypothesized and recently applied diagnostic criteria involving CK7 and CK20 immunoreactivity are not reliable in distinguishing short-segment Barrett esophagus from intestinal metaplasia as seen in gastric cardia and corpus.

A multicenter, randomized, prospective study of 14-day ranitidine bismuth citrate- vs. lansoprazole-based triple therapy for the eradication of Helicobacter pylori in dyspeptic patients.

BACKGROUND/AIMS: Proton-pump inhibitor and ranitidine bismuth citrate-based triple regimens are the two recommended first line treatments for the eradication of Helicobacter pylori. We aimed to compare the effectiveness and tolerability of these two treatments in a prospective, multicentric, randomized study. MATERIALS AND METHODS: Patients with dyspeptic complaints were recruited from 15 study centers. Presence of Helicobacter pylori was investigated by both histology and rapid urease test. The patients were randomized to either ranitidine bismuth citrate 400 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=149) or lansoprazole 30 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=130) treatment arm for 14 days. Adverse events have been recorded during the treatment phase. A 13 C urea breath test was performed 6 weeks after termination of treatment to assess the efficacy of the therapy. Eradication rate was calculated by intention-to-treat and per-protocol analysis. RESULTS: Two hundred seventy-nine patients (123 male, 156 female) were eligible for randomization. In per-protocol analysis (n=247), Helicobacter pylori was eradicated with ranitidine bismuth citrate- and lansoprazole-based regimens in 74,6% and 69,2% of cases, respectively (p>0,05). Intention-to-treat analysis (n=279) revealed that eradication rates were 65,1% and 63,6% in ranitidine bismuth citrate and in lansoprazole-based regimens, respectively (p>0,05). Both regimes were well-tolerated, and no serious adverse event was observed during the study. CONCLUSION: Ranitidine bismuth citrate-based regimen is at least as effective and tolerable as the classical proton-pump inhibitor-based regimen, but none of the therapies could achieve the recommendable eradication rate.

Serum progranulin as an independent marker of liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease.

BACKGROUND: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics. SUBJECTS AND METHODS: We measured serum progranulin levels in 95 patients with biopsy-proven NAFLD and 80 age- and sex-matched controls. The potential associations between progranulin and the characteristics of NAFLD patients were examined by multiple linear regression analysis. RESULTS: Serum progranulin levels were significantly higher in NAFLD patients (34 ± 13 ng/mL) than in controls (28 ± 7 ng/mL, P < 0.001). In NAFLD patients, serum progranulin levels were associated with lipid levels and the degree of hepatic fibrosis. After adjustment for potential confounders, serum progranulin remained an independent predictor of the degree of hepatic fibrosis in NAFLD patients (ß = 0.392; t = 2.226, P < 0.01). CONCLUSIONS: Compared with controls, NAFLD patients have higher serum progranulin concentrations, which are closely associated with lipid values and the extent of hepatic fibrosis.

Serum levels of vaspin, obestatin, and apelin-36 in patients with nonalcoholic fatty liver disease.

The novel adipokines vaspin, obestatin, and apelin-36 are associated with insulin resistance and the components of the metabolic syndrome. We assayed circulating levels of these molecules and examined their association with clinical, biochemical, and histologic phenotypes in patients with nonalcoholic fatty liver disease (NAFLD). Serum levels of vaspin, obestatin, and apelin-36 were assayed by enzyme-linked immunosorbent assay in 91 patients with biopsy-proven NAFLD and 81 controls. We analyzed associations between adipokines and the characteristics of patients with NAFLD using multivariable linear regression models. Univariable analysis showed that concentrations of vaspin and apelin-36 were significantly higher in patients with NAFLD than in controls, whereas no differences in obestatin levels were found. Serum vaspin levels showed a statistically significant association with C-reactive protein (r = 0.378, P < .001) and liver fibrosis scores (r = 0.401, P < .001), whereas apelin-36 levels showed a modest association with homeostasis model assessment of insulin resistance (r = 0.204, P < .01). After stepwise linear regression analysis, serum vaspin levels were the only independent predictor of liver fibrosis scores in patients with NAFLD (ß = 0.37, t = 3.99, P < .01). Serum vaspin levels are raised in patients with NAFLD regardless of potential confounders and represent an independent predictor of liver fibrosis scores. These findings support further investigation of this novel adipokine in metabolic liver diseases.