SAHA induce hippo pathway in CCA cells without increasing cell proliferation.

BACKGROUND: Cholangiocarcinoma is a malignant tumor originating from bile duct epithelial cells. Since tumor metastasis is associated with poor prognosis and short-term survival of patients, there is an urgent need for alternative therapeutic approaches for CCA. Because of that reason, we aimed to investigate effect of SAHA which is known as HDAC inhibitor on extrahepatic cholangiocarcinoma cell line (TFK-1). METHODS: Cell cycle was measured by Muse Cell Analyzer. YAP, TAZ, TGF-ß protein levels were determined by western-blotting method. TEAD (1-3), TIMP2 and TIMP3 genes level were determined by real-time PCR analysis. RESULTS: We have seen the positive effects of SAHA on the TFK-1 cell line as it reduces cell viability and arresting cells in the G0/G1 phase. We also observed the negative effects of SAHA, as it increases the expression levels of YAP, TAZ, TGF-ß protein and TEAD (1-3) gene. We also found that SAHA reduced the expression levels of TIMP2 and TIMP3 in TFK-1 cells, but was not statistically significant. CONCLUSIONS: Although observing its antiproliferative effects, these negative effects may be related to the cells being resistant to the drug or the remaining cells having a more aggressive phenotype. Therefore, we think that caution should be exercised in the use of this drug for CCA treatment.

The role of TNF-α and PAI-1 gene polymorphisms in familial Mediterranean fever.

OBJECTIVES: Familial Mediterranean fever (FMF) is one of the most serious inherited inflammatory disorders among Jewish, Armenian, Turkish and Arab populations. The imbalance between pro- and anti-inflammatory cytokines may play a role in its etiology. We have investigated whether tumor necrosis factor-alpha (TNF-α) and plasminogen activator inhibitor 1 (PAI-1) gene polymorphisms are associated with FMF and evaluated the relationship between these polymorphisms and genotypic manifestation of FMF. METHODS: We investigated single nucleotide polymorphisms of the TNF-α promoter at positions -308 G/A and the PAI-1 4G/5G gene polymorphism in peripheral blood leukocytes collected from 177 individuals with FMF with different genotype combinations. All of the polymorphisms of TNF-α and PAI-1 were detected by PCR and restriction fragment length polymorphism analysis. RESULTS: There were no association between the TNF-α/308 genotypes and mutations in FMF. In contrast, the PAI-1 4G/5G gene polymorphism may have a significant effect in FMF disease. CONCLUSIONS: Screening with PAI-1 gene polymorphism tests may be beneficial for tracing future FMF patients. However, further investigations are needed to reach a conclusion on the association between PAI-1 polymorphisms and FMF.

Paraoxonase is reduced in patients with growth hormone deficiency: A novel risk factor for atherosclerosis.

BACKGROUND: Growth hormone deficiency (GHD) is associated with an increased cardiovascular mortality. Increased oxidative stress has been associated with development of cardiovascular and cerebrovascular diseases. In the present study, we aimed to evaluate oxidant and antioxidant status in patients with GHD by analyzing serum paraoxonase1 (PON1) activity, and malondialdehyde (MDA) and thiol levels. MATERIALS AND METHODS: This study was a case-control study. Thirty patients with GHD were included in the study and compared with 20 healthy controls. Serum PON1 activity, and MDA and thiol levels were measured according to an enzymatic spectrophotometric method. RESULTS: Serum MDA levels (2.8 ± 1.3 nmol/mL) were higher in GHD group than the controls (1.7 ± 0.5 nmol/mL) (P = 0.001). PON1 activity (149.9 ± 77.9 U/L) was lower in GHD group than the controls (286.3 ± 126.7 U/L) (P = 0.001). Thiol and high-density lipoprotein cholesterol (HDL-cholesterol) levels were lower in GHD group (218.6 ± 103.9 µmol/L and 32.6 ± 13.4 mg/dL, respectively) than the controls (289.6 ± 101.1 µmol/L and 54.3 ± 14.9 mg/dL, respectively) (P = 0.021 and P = 0.001, respectively). In GHD patients, serum MDA level was negatively correlated with serum HDL-cholesterol (r = -0.499, P = 0.001), and serum PON1 activity was positively correlated with serum thiol and HDL-cholesterol levels (r = 0.306, P = 0.032 and r = 0.303, P = 0.033, respectively). CONCLUSION: These data support that GHD is characterized by an imbalance between oxidant and antioxidant factors. This abnormality may contribute to the increased atherogenic risk in patients with GHD.

Investigation of genome instability in exfoliated colonic epithelial cells and in mitogen-stimulated lymphocytes of patients with ulcerative colitis.

OBJECTIVE: The present study aimed to evaluate the micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in the mitogen-stimulated lymphocytes of patients with ulcerative colitis (UC). In addition, we assessed MN frequency in exfoliated colonic epithelial cells obtained from both the diseased and healthy colonic mucosa of patients. DESIGN: The study was conducted in 22 newly diagnosed patients with UC and in 22 healthy controls. MN, NPB and NBUD values scored in binucleated (BN) cells were obtained from the mitogen-stimulated lymphocytes of patients and control subjects. In addition, the MN values in exfoliated epithelial cells obtained from the diseased and healthy colonic mucosa of patients were evaluated. RESULTS: We found significantly higher MN, NPB and NBUD frequencies in the BN cells of patients with UC than in those of the control subjects (1.61 ± 0.75 vs. 0.89 ± 0.29, 3.93 ± 1.91 vs. 1.39 ± 1.10, and 1.55 ± 0.89 vs. 0.64 ± 0.48, p = 0.001). Also, a statistically significant difference was found between MN frequencies obtained from the diseased and healthy colonic mucosa of patients (1.07 ± 0.46 vs. 0.59 ± 0.21, p = 0.001). No significant relationship was found between age and MN frequency in patients with UC (r = 0.076, p = 0.735). CONCLUSION: Increased MN, NPB and NBUD frequencies observed in both the lymphocytes and exfoliated colonic epithelial cells obtained from patients with UC may reflect genomic instability.

If AFP is elevated, where is cancer? The case report on hereditary persistence of Alpha-fetoprotein.

Alpha-fetoprotein (AFP) is expressed by tumors with a high mitotic index such as hepatocellular carcinoma and germ cell tumors, therefore it is used as a tumor biomarker. Interestingly, although there is no underlying cause, elevated AFP has been reported in some genetically predisposed individuals. This is a very rare and benign condition called "hereditary persistence of AFP (HPAFP)" and an inherited in an autosomal dominant manner. To our knowledge, only 28 families have been reported to date. Some of the reported cases received inappropriate treatments such as chemotherapy and surgery. The possibility of HPAFP should be kept in mind in patients with high AFP in the absence of radiological evidence of hepatocellular carcinoma or germ cell tumor to avoid harmful procedures. It can be easily confirmed by analyzing AFP levels in other family members. We report a case of HPAFP with surprisingly higher AFP levels than previously reported cases and this is the first case reported from Turkey.

Common Familial Mediterranean Fever gene mutations in a Turkish cohort.

Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder with the responsible gene of MEFV which primarily affects Jewish, Armenian, Turkish and Arab populations. The FMF gene (MEFV) has recently been cloned to chromosome 16 p, which encodes pyrin. In the present study, we enrolled 2,067 unrelated patients with the suspicion of FMF in Middle Anatolia between the years 2006-2009 and identified the 12 MEFV mutations. DNA was amplified by PCR and subjected to reverse hybridization for the detection of MEFV gene mutations. Among the 2,067 patients, 866 (41.9%) were males and 1,201 (58.1%) were females. The mutations were homozygous in 176 (16.85%) patients, compound heterozygous in 314 (30.1%) patients, heterozygous in 546 (52.25%) patients and the other forms of mutations were found in 8 patients (0.76%). No mutation was detected in 1,023 (49.5%) patients. The most frequent mutations were M694V, M680I (G/C), E148Q and V726A. We could not find any significant differences between the two common mutations according to the gender. The high incidence of MEFV gene mutations in the Turkish population indicated that newborn screening may be discussed in the future. Because of the ethnic origin of Anatolia, larger serial analyses are necessary to investigate the rate and coexistence of these mutations.

Macrolipasemia secondary to colon cancer chemotherapy: a case report.

We reported macrolipasemia in a colon cancer patient during the chemotherapy period without any evidence of pancreatitis. A 52-year-old man formerly treated for papillary thyroid carcinoma had elevated a carcinoembryonic antigen (CEA) concentration in the latest control and was diagnosed with colon cancer. Xelox chemotherapy (oxaliplatin and capecitabine) protocol was planned for six months. Interestingly, the lipase activities gradually increased from 30 U/L to 434 U/L, and exceeded three times the upper limit of the reference range (13-60 U/L). There were no symptoms of pancreatitis, and the abdominal computed tomography (CT) scan was also normal. Polyethylene glycol (PEG) recovery % values of serum samples gradually decreased and were 27% in the recent sample before the end of chemotherapy. Interestingly, the serum lipase activity fell a month after chemotherapy, and PEG recovery % increased (39%). We considered the following possibilities: (1) macrolipasemia due to chemotherapy drugs, (2) macrolipasemia due to antibodies against chemotherapy drugs.

Suberoylanilide Hydroxamic Acid (SAHA) Reduces Fibrosis Markers and Deactivates Human Stellate Cells via the Epithelial-Mesenchymal Transition (EMT).

Hepatic fibrosis is known as the accumulation of connective tissue secondary to chronic damage to the liver. Epithelial-mesenchymal transition (EMT) corresponding increase in liver fibrogenesis was shown with immunohistochemistry and PCR-based studies. Suberoylanilide hydroxamic acid (SAHA), a synthetic compound approved as a histone deacetylase inhibitor (HDAC) by the FDA to treat cutaneous T-cell lymphoma is under investigation for the treatment of lung and renal fibrosis. Experimental modeling for hepatic fibrosis can be constructed with an LX2 cell line isolated from human hepatic stellate cells (HSCs). In this study, we aimed to investigate the modulation of SAHA in the pathogenesis of liver fibrosis by detecting the levels of proteins; (E-cadherin (E-cad), N-cadherin (N-cad), Vimentin (Vim), and genes; E-cad, N-cad, Vim, transforming growth factor-beta (TGF-ß), alpha-smooth muscle actin (α-SMA), type 1 collagen (COL1A1), type 3 collagen (COL3A1)) that play a significant role in EMT with the LX2 cell line. We also evaluated the action of SAHA with cell proliferation, clonogenic, and migration assay. Cell proliferation was performed by flow cytometry. All the protein levels were determined by Western blot analysis, and gene expression levels were measured by Real-Time PCR. Our study observed that SAHA treatment decreased cell viability, colony formation and migration in LX2 cells. We found that SAHA increased E-cad expression level, while it decreased N-cad, Vim, COL1A1, COL3A1, α-SMA TGF-ß genes expression levels. SAHA decreased the level of E-cad, N-cad, and Vim protein levels. We thought that SAHA possesses potent antifibrotic and anti-EMT properties in LX2.

The Effect of EZH2 Inhibition through DZNep on Epithelial-Mesenchymal Transition Mechanism.

Although the molecular pathogenesis of hepatocellular carcinoma (HCC) is uncertain, it is known that the epithelial-mesenchymal transition (EMT) mechanism and epigenetic changes have an important role. This study was focused on evaluating the relationship of 3-Deazaneplanocin A (DZNep) with the EMT mechanism, which is a histone methyltransferase inhibitor on HCC and is also known as an enhancer of zeste homolog 2 (EZH2) inhibitor. Cell viability of HepG2 cells (HCC cell line) assessed for DZNep over 72 hours with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, colony-forming assay, apoptosis assay, RNA isolation, cDNA synthesis, and real-time PCR (RT-PCR) were performed to see the effect of DZNep on HepG2 cells. DZNep reduced cell proliferation for 72 hours, also significantly reduced colony formation in addition it increased the total apoptosis. DZNep on EZH2, E-cadherin, N-cadherin, and Vimentin (Vim) gene expressions was given different results by either decreasing or increasing the expressions. In this study, we observed a positive effect of DZNep on apoptosis and TIMP3 expression level and decreased colony formation. However, it gave complicated results with the level of gene expression E-cadherin and TIMP2, increase the level of Vim and MMP2 expression. Therefore, we think that further studies are necessary to clarify the role of DZNep.

Advanced oxidation protein products: a novel marker of oxidative stress in ulcerative colitis.

BACKGROUND/GOALS: The etiology and pathogenesis of chronic inflammatory bowel diseases are still poorly understood. Oxidative stress takes place in the pathogenesis of ulcerative colitis (UC) and advanced oxidation protein products (AOPP) are accepted as a novel marker of oxidative stress. There are no data concerning whether AOPP may be used as a simple serum marker to assess the disease activity, predict severity of the disease course in UC. STUDY: In this study, we determine the importance of neutrophil activation and the role of oxidative stress in the pathogenesis of UC, by quantification of AOPP and total thiol levels as markers of oxidative protein damage, malondialdehyde levels as a marker of lipid peroxidation, and myeloperoxidase activity as a marker of neutrophil activation in patients with UC. RESULTS: Serum levels of AOPP, thiol, myeloperoxidase activity, and malondialdehyde were found as increased in UC group compared with controls (P=0.004, 0.047, 0.001, and 0.001 respectively). CONCLUSIONS: Our finding of increased levels of plasma AOPP levels supports the presence of oxidative stress and protein oxidation in UC and this marker may be used as a simple serum marker to assess disease activity, predict the severity of disease course, and perhaps response to therapy.

Is increased colon subepithelial collagen layer thickness in diabetic patients related to collagenous colitis? An immunohistochemical study.

In this study, we evaluated immunohistochemically whether increased thickness of the colon subepithelial collagen layer in diabetic patients relates to collagenous colitis. A total of 100 patients (25 in each group) were included in this study. There were diabetic patients with chronic diarrhea in the first group, diabetic patients without chronic diarrhea in the second group, non-diabetic patients with chronic diarrhea in the third group, and control patients in the fourth group. The endoscopic biopsy specimens were obtained from the rectum, sigmoid colon, and descending colon. The thickness of the subepithelial collagen layer was measured using the ocular micrometer method. The immunohistochemical staining was performed with type 1 collagen and fibronectin antibody. The thickness of the colon subepithelial collagen layer in diabetic patients with or without diarrhea was significantly greater than that in control patients. This thickened subepithelial collagen layer in diabetic patients was stained with fibronectin antibody, but not with type 1 collagen antibody in the immunohistochemical study. These immunohistochemical staining characteristics were not similar to those in collagenous colitis, but were similar to those in normal subjects. Increased colon subepithelial collagen layer thickness in diabetic patients does not relate to collagenous colitis.

How the I1307K adenomatous polyposis coli gene variant contributes in the assessment of risk of colorectal cancer, but not stomach cancer, in a Turkish population.

Germline and somatic truncating mutations of the adenomatous polyposis coli gene (APC) are thought to initiate colorectal tumor formation in familial adenomatous polyposis syndrome and sporadic colorectal carcinogenesis, respectively. Recently, an isoleucine-lysine polymorphism at codon 1307 (I1307K) of the APC gene has been identified in 6-7% of the Ashkenazi Jewish population. To assess the risk of this common APC allelic variant in colorectal carcinogenesis, a cohort of unselected Turkish subjects with stomach or colorectal cancer (or both) was analyzed for the APC I1307K polymorphism. Genomic DNA was extracted from patients by obtaining all stomach and colon malign polipose tissues using nuclei lysis methods. Detection of the I1307K mutation was performed using the commercial Pronto APC kit according to the manufacturer's instructions. The APC I1307K allele was identified in 7 of 57 stomach carcinoma patients (12.3%; P > 0.05) and 30 of 56 colon carcinoma patients (53.6%; P < 0.05) using antigen-anticor interaction methods. Comparing the frequencies of the two separate population control groups, the APC I1307K allele is associated with an estimated relative risk of 1.9 for colorectal neoplasia. Furthermore, APC I1307K carriers had greater numbers of adenomas and colorectal cancers per patient than noncarriers. The conclusion is that the APC I1307K variant leads to increased adenoma formation and colorectal cancer. The estimated relative risk for carriers may justify specific clinical screening for Turkish people expected to harbor this allele, and genetic testing in the long term may significantly promote colorectal cancer prevention in this population.

Oxidative stress and antioxidant defenses in serum of patients with non-alcoholic steatohepatitis.

OBJECTIVES: Oxidative stress is an important pathophysiological mechanism in non-alcoholic steatohepatitis (NASH). We aimed to evaluate serum xanthine oxidase (XO) (as a generator of reactive oxygen species), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), paraoxonase (PON1) activities, nitric oxide (NO) and thiol levels in patients with NASH. DESIGN AND METHODS: A total of 35 patients with NASH and 31 age-and-gender-matched healthy subjects were enrolled in the study as control group. Serum levels of XO, NO, SOD, GSHPx, PON1 and thiol were determined by spectrophotometric methods. RESULTS: Serum XO activities were higher in the patients with NASH than the controls (p<0.001). Serum NO levels, SOD, GSHPx, PON1 activities and thiol levels were lower in the patients with NASH than the controls (p<0.031, p<0.019, p<0.001, p<0.001, p<0.001, respectively). CONCLUSIONS: Increased oxidative stress in patients with NASH may result in a pro-oxidation environment, which in turn could result in decreased antioxidant enzyme activities and NO levels. Therefore effective antioxidant therapy to inhibit oxidative stress is necessary and agents to increase antioxidant enzyme may be a therapeutic option in NASH.

Pyoderma gangrenosum and exacerbation of psoriasis resulting from pegylated interferon alpha and ribavirin treatment of chronic hepatitis C.

Interferon therapy is the cornerstone of chronic hepatitis C treatment. Side effects of interferon include possible triggering or exacerbation of immune diseases in consequence of immunomodulatory effects. We describe the unique case, in which pyoderma gangrenosum and exacerbation of psoriasis were developed 8 weeks after pegylated interferon alpha 2a and ribavirin therapy in a 45-year-old woman. The therapy had to be stopped on account of pyoderma gangrenosum and exacerbation of psoriasis in spite of a biochemical response to the therapy for hepatitis C. The evolution was favorable after stopping treatment. Therefore, we propose this would suggest a possible autoimmune mechanism for the development of pyoderma gangrenosum and exacerbation of psoriasis with pegylated interferon therapy. A susceptible patient, who has an autoimmune disease before interferon therapy, had to be informed that interferons may induce de novo or exacerbate existing immune diseases by immunomodulatory actions. To the best of our knowledge, this is the first case report of pyoderma gangrenosum and psoriasis that resulted from pegylated interferon alpha 2a and ribavirin treatment of chronic hepatitis C.

Clostridium difficile infection frequency in patients with nosocomial infections or using antibiotics.

BACKGROUND/AIMS: Clostridium difficile is the most common cause of nosocomial infectious diarrhea. The frequency of colonization in hospitalized patients varies between 10 and 43%. METHODOLOGY: Clostridium difficile common antigen was investigated in stool samples of 50 patients who developed nosocomial diarrhea (group 1), 65 outpatients who attended the clinic after development of diarrhea during antibiotic use (group 2), 18 patients with active chronic inflammatory bowel disease (group 3), and 30 control patients were studied. The Latex agglutination test and the toxin A was performed to investigate the presence of the Clostridium difficile common antigen in stool samples. The possible predisposing factors for nosocomial infection were analyzed. RESULTS: Clostridium difficile common antigen was found positive in 27.7% and 14% of group 2 and group 1, respectively while negative in stools of patients with inflammatory bowel disease. Asymptomatic fecal Clostridium difficile carriage in healthy volunteers was 3.3%. The antibiotic that induced diarrhea the most was clindamycin in group 1, and ampicillin-sulbactam in group 2. Enema was found to be the most important risk factor for C. difficile in hospitalized patients. CONCLUSIONS: The Clostridium difficile common antigen was detected more frequently in antibiotic-associated diarrhea patients than in nosocomial diarrhea patients. Clostridium difficile-associated diarrhea was also more frequent in immunosuppressive patients with uremia and diabetes mellitus.

Ipilimumab-associated cholestatic hepatitis: a case report and literature review.

Ipilimumab is a monoclonal antibody that exerts its effects by inhibiting the cytotoxic T-lymphocyte-associated protein 4 receptor on cytotoxic T lymphocytes. It is frequently used for the treatment of unresectable or metastatic melanoma. Ipilimumab may lead to several immune-related disease including colitis, thyroiditis, pneumonia, hepatitis, or pancreatitis as a side effect. Limited number of cases with hepatic damage as an ipilimumab-related adverse event has been reported in the literature. This agent has been implicated in causing acute hepatitis-like liver injury. Here, we presented a case in which cholestatic hepatitis developed during ipilimumab use for the treatment of metastatic melanoma.

Adrenal axis functions in patients with familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is a hereditary disease characterized by recurrent attacks of fever with peritonitis, arthritis, pleuritis or erysipelas-like rash. It is unclear what effects of FMF itself on endocrine system and hormones are. None of the FMF patients without amyloidosis have been reported to have any endocrine disorders, except those who developed colchicine-induced diabetes insipidus. There is a large body of evidence to show that cytokines (IL-1, IL-6 and TNF-alpha) activate the hypothalamic-pituitary-adrenal (HPA) axis. We have designated this study to investigate the HPA axis in FMF patients without amyloidosis. METHODS: Twenty-one patients with FMF were included. ACTH stimulation test was performed on the healthy subjects and during attack period in the patients. In the patient group, same test was repeated during remission period. RESULTS: Peak cortisol levels were significantly higher in the attack period than those in the remission period of patients (p<0.05). CONCLUSION: The cytokines play a role on the activation of the HPA axis; we thought the axis would be affected in this disease. The response of cortisol to 250 mug ACTH was significant in attack period when compared with remission period. This result reveals that HPA axis is more activated in an FMF attack. Previous studies suggest that the adrenal hormones increase in acute inflammatory events, and eventually, the changes on these hormones are related to TNF and IL-6 levels. During the FMF attack, HPA axis may be stimulated by cytokines. It seems that HPA axis is regulated normally in FMF patients.

Assessment of paraoxonase 1 activity and malondialdehyde levels in patients with rheumatoid arthritis.

OBJECTIVES: We aimed to evaluate antioxidant paraoxonase 1 activity together with malondialdehyde (MDA) (an oxidative stress parameter) levels in patients with rheumatoid arthritis. DESIGN AND METHODS: Fifty-seven rheumatoid arthritis patients were included in the study and subgrouped according to disease activity (active, n = 31; inactive, n = 26) and compared with healthy controls (n = 25). Serum paraoxonase 1 activity and MDA levels were measured according to an enzymatic spectrophotometric method. RESULTS: Serum MDA level was higher (P = 0.001) whereas paraoxonase 1 activity was lower (P = 0.001) in the patient group than the controls. When active and inactive subgroups were compared with the control group, there was a statistically significant difference between each parameter. Serum MDA levels were significantly higher, while paraoxonase 1 activity was lower in the active and inactive rheumatoid arthritis groups than the control group. But there was not any difference between active and inactive patients with RA. There was a negative correlation between MDA levels and paraoxonase 1 activity. CONCLUSIONS: Increased reactive oxygen species levels in rheumatoid arthritis may result in a pro-oxidation environment, which in turn could result in decreased antioxidant paraoxonase 1 activity and increased MDA levels.

A new marker for lipid peroxidation: serum paraoxonase activity in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: Relationship between hepatic antioxidant paraoxonase 1 (PON1) activity, lipid peroxidation and liver injury was investigated in patients with non-alcoholic steatohepatitis. METHODS: A total of 23 patients with non-alcoholic steatohepatitis (15 males, 8 females; mean age: 40.30+/-7.67 yrs) and 23 healthy controls (14 males, 9 females; mean age: 39.70+/- 8.78 yrs) were enrolled in the study. Serum paraoxonase 1 activity and levels of a well-known lipid peroxidation marker, serum malondialdehyde, were determined. RESULTS: Serum paraoxonase 1 activity decreased significantly in non-alcoholic steatohepatitis compared to the control group (p<0.01). Serum malondialdehyde levels were significantly higher in patients with non-alcoholic steatohepatitis as compared with the control group (p<0.05). No statistically significant correlations were found between serum paraoxonase 1 activities and the grade-stage of non-alcoholic steatohepatitis, serum lipid levels or serum malondialdehyde levels (p>0.05). CONCLUSIONS: Increased lipid peroxidation may be either a cause or a result of liver injury in patients with non-alcoholic steatohepatitis. Although serum paraoxonase 1 activity does not reflect the degree of liver damage in non-alcoholic steatohepatitis, reduced paraoxonase 1 activity, especially in the presence of mild disease, could be interpreted as a biochemical marker of the lipid peroxidation.