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© 2023 Pan-Arab Association of GastroenterologyBackground and study aims: Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for chronic kidney disease (CKD). Previous studies argued that leptin levels increase significantly with the progression of CKD. But the association between leptin and CKD has not been investigated in patients with NAFLD. Therefore, we conducted this study to establish whether increased leptin level is associated with CKD in NAFLD patients. Patients and methods: In our prospective study with a follow up period of six months thirty-five teetotaller biopsy-proven NAFLD patients were divided as groups with mild, versus advanced, fibrosis. Liver fibrosis was also assessed with Fibroscan. Serum leptin levels were measured by radioimmunoassay. For insulin resistance we used the homeostasis model assessment method (HOMA-IR). For the kidney function, we used the abbreviated formula Modification of Diet in Renal Disease (MDRD) formula, which estimates GFR. For statistical analysis, Student\"s-t test, Mann-Whitney test, linear regression-binary logistic regression analyses and the ROC curve analysis were used. Results: Advanced fibrosis and increased HOMA-IR were risk factors for decreased eGFR. Leptin correlated inversely with advanced fibrosis (p: 0.03) and low leptin was a risk factor for CKD (p: 0.02). In ROC curve analysis, advanced fibrosis and low leptin were risk factors for decreased eGFR (p: 0.007 and 0.004, respectively). Low leptin level was dependently associated with decreased eGFR. Conclusion: Advanced fibrosis in NAFLD patients is a risk factor for CKD. Leptin correlated inversely with advanced fibrosis. Unlike the previous studies, which were not performed in NAFLD patients, we found decreased leptin in NAFLD patients with decreased eGFR. Low leptin level was found to be a dependent predictor for differentiating NAFLD patients with high risk for CKD.

Hepatitis C is one of the leading causes of death in patients with inherited bleeding disorders. Currently, direct-acting antiviral drugs used for the treatment of hepatitis C have become an effective and a reliable option for people with inherited bleeding disorders. The aim of this study is to report the efficacy and safety of ombitasvir + paritaprevir/ritonavir and dasabuvir combination in the treatment of hepatitis C in patients with inherited bleeding disorders.In this retrospective study, we evaluated the efficacy and safety of the combination of ombitasvir + paritaprevir/ritonavir and dasabuvir in 10 adult patients with hemophilia A, 4 patients with hemophilia B, and 1 patient with von Willebrand disease who were infected with hepatitis C genotype 1.Five patients had genotype 1a and 10 patients had genotype 1b chronic hepatitis C. One patient had Child A cirrhosis, 14 patients had chronic hepatitis C without cirrhosis. Hepatitis C virus ribonucleic acid was negative in all patients at week 4 and at the end of the treatment. Sustained virologic response was obtained in all patients. Serious side effects were detected in 3 patients, which were intra- muscular bleeding, erosive gastritis-related gastrointestinal bleeding, and pneumonia.Ombitasvir + paritaprevir combined with ritonavir and dasabuvir ± ribavirin is an effective treatment for patients infected with genotype 1 hepatitis C who have coagulation disorders. Tolerance and side effects are similar to other treatment options.

Objective In this study, we aimed to investigate the effects of direct antiviral treatment on depression, anxiety, fatigue and quality of life in patients with chronic hepatitis C. Methods Subjects included in study were treatment experienced and treatment naive chronic hepatitis C patients admitted to the hepatology outpatient clinic between December 2016 and June 2017. Before and after the treatment, Beck depression, Beck anxiety, liver-specific quality of life and fatigue severity-impact scales were administered. Descriptive statistical methods, Kolmogorov-Smirnov distribution test Wilcoxon sign and kappa coefficient tests were used to evaluate the study data. Results Forty-four patients were included in the study; however, it was completed with 35 patients only, as some of the patients were excluded for various reasons. There was no significant difference between depression and anxiety scores of the patients before and after the treatment, but depression and anxiety were found to be recovered in 28.5% (4/14) and 23.5% (4/17) of the subjects, respectively. At the end of the treatment, fatigue severity-impact scales and liver-specific quality of life were not significantly different from those before the treatment. Conclusion In this study, we found that direct antivirals did not lead to depression, anxiety or fatigue and did not decrease liver-specific quality of life. In some cases, depression and anxiety decreased after the treatment.

Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). We evaluated whether IR contributes to hepatocyte apoptosis, inflammation, and fibrosis in NAFLD.Forty-four teetotaller patients with biopsy-proven diagnosis of NAFLD were enrolled. Twenty-eight NAFLD patients with IR were compared with 16 subjects without IR. For apoptotic activity caspase 3 and 8, transcription nuclear factor kB (NF-kB), and anti-apoptotic Bcl-2 protein were determined through immunohistochemical methods.HOMA-IR index was significantly correlated with the stage and caspase 3- and 8 levels (p= 0.001, 0.02, and 0.01, respectively). HOMA-IR index was independently associated with the severity of fibrosis ( = 5.9, p = 0.001), caspase-3 ( = 0.16, p = 0.001), and caspase-8 (b =0.032, p = 0.018) levels. TNF-sRp55 level was positively correlated with HOMA-IR index (p = 0.024). Patients with IR had significantly higher necroinflammatory grade, stage, caspase-3, and caspase-8 levels than those without IR (p = 0.022, 0.007, 0.031, and p = 0.011, respectively). HOMA-IR index had statistically significant values for distinguishing of severe necroinflammatory grade, stage and for differentiating NASH from simple fatty liver (AUC = 0.78, 0.76, and 0.82, respectively).This study demonstrates that IR in NAFLD is associated with enhanced hepatocyte apoptosis and histopathologic disease severity. These data indicate that NAFLD patients with IR may have increased risk for disease progression.

63rd Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease (AASLD) -- NOV 09-13, 2012 -- Boston, MA WOS: 000353553700026 PubMed ID: 25910292 Background/Aims: We investigated the risk of abdominal operation in patients with fatty liver and the risk of any cancer in first-degree relatives of patients with fatty liver. Materials and Methods: We evaluated 105 patients with nonalcoholic fatty liver disease (NAFLD), 121 patients with biopsy-proven hepatitis C (61 patients with fatty liver and 60 patients without fatty liver), 50 patients with inflammatory bowel disease (IBD), and 109 patients with dyspepsia. Results: There was no difference in sex, mean age, and marital status among the groups except that patients with IBD were younger than the others (p

Background/aims Oxidative stress and insulin resistance (IR) are major contributors in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to find the relation between oxidative stress parameters and histopathological findings in NAFLD patients with and without insulin resistance (IR). Materials and methods Thirty-two patients with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied (M/F: 17/15; mean age 46.5±11.4 years). Twenty-one NAFLD patients with IR were compared with 11 patients without IR. The fasting insulin level was measured, and the insulin resistance index was calculated using the homeostasis model assessment (HOMA) method. Malondialdehyde (MDA) and superoxide dismutase (SOD) activities were measured in tissue and serum specimens. Glutathione (GH) was measured in tissue homogenates. Nitric oxide (NO), vitamin E and C levels were measured in serum. Results Patients with IR had significantly higher tissue MDA levels (p=0.001) and significantly decreased tissue SOD and GH levels (p=0.001 and 0.002, respectively) than those without IR. The steatosis grade, necroinflammatory grade and stage were significantly higher in patients with IR (p=0.035, 0.003 and 0.001, respectively). HOMA IR significantly correlated with the necroinflammatory grade, stage, tissue MDA, SOD and GH (p=0.013, 0.001, 0.008, 0.001 and 0.001, respectively). Serum MDA (β=1.88, p=0.002), serum SOD (β=0.57, p=0.006), tissue MDA (β=0.22, p=0.006), tissue SOD (β=1.48, p=0.071) and stage (β=2.81, p=0.003) were independently associated with increased HOMA IR. Increased MDA [OR: 1.51; 95% CI: (1.03-2.22); p=0.034] was a risk factor for non-alcoholic steatohepatitis (NASH), and increased SOD activity had a preventive effect against NASH [OR: 0.008; 95% CI: (0.001-0.98); p=0.04]. Conclusion This study shows that insulin resistance in NAFLD correlates with enhanced oxidative stress. Histopathological disease severity significantly correlated with oxidative stress parameters. These data show that NAFLD patients with IR may have increased risk for disease progression.

BACKGROUND/AIMS Several guidelines recommend the use of tenofovir or entecavir as the first-line treatment for hepatitis B due to the lower resistance rates of these drugs than lamivudine, although lamivudine may still be preferred because of its low adverse effect profile and cost. It is important to know which patients might benefit from lamivudine as the first-line treatment. We aimed to assess the success rates of lamivudine, entecavir, and tenofovir, as well as the resistance rates, frequencies of HBsAg clearance, and risk factors for lamivudine resistance. MATERIALS AND METHODS A total of 191 patients with chronic HBeAg-negative hepatitis who were treated with lamivudine, entecavir, or tenofovir were included. Predictors of resistance to lamivudine were analyzed. RESULTS The cumulative first-, second-, third-, fourth-, and fifth-year rates of virologic breakthrough during extended lamivudine therapy were 24%, 30%, 38%, 46%, and 54%, respectively. The rate of undetectable DNA at the 60th month of those who took lamivudine was 51%. Cox regression analysis revealed that positive HBV DNA at the sixth month (HR=15; 95% CI: [7.1-33], p=0.001), being aged 41 years or more (HR=3.4; 95% CI: [1.8-6.4], p=0.001), and baseline HBV DNA of 170,500 IU/mL or higher (HR=2.1; 95% CI: [1.2-3.7], p=0.01) were independently associated with the development of resistance to lamivudine. CONCLUSION In HBeAg-negative chronic hepatitis B, baseline serum hepatitis B virus DNA levels exceeding 170,500 IU/mL, partial virologic response in the sixth month, and age of 41 years or more were independent predictors for virologic breakthrough. Moreover, 2% of these patients cleared HBsAg.

Background: Liver biopsy is an imperfect gold standard for assessing the disease severity in hemodialysis patients with chronic hepatitis C. Our purpose was to compare the accuracy of the FibroTest (FT) and ActiTest (AT) with liver biopsy and the AST-to-platelet ratio index (APRI) in determining hepatic fibrosis and necroinflammatory activity in hemodialysis patients with hepatitis C virus (HCV). Methods: The FT-AT index combining 6 biochemical markers was assessed in 33 hemodialysis patients with HCV. Liver fibrosis and necroinflammatory activity was staged and graded according to the METAVIR scoring system. Results: The accuracy of FT-AT versus biopsy was 0.46 for significant fibrosis and 0.36 for severe necroinflammatory activity. The FT index had a positive predictive value of 20% for scores greater than 0.6 and a negative predictive value of 45% for scores less than 0.2. Eleven of the 33 patients had scores ≤0.2, 6 had significant fibrosis on biopsy. Four out of 5 patients with FT scores >0.6 had mild fibrosis. APRI correlated well with the biopsy. Conclusion: The FT-AT test does not seem to be a reliable noninvasive marker for the prediction of necroinflammatory activity and fibrosis in hemodialysis patients with HCV and cannot be used as an alternative to either liver biopsy or APRI.

Aim: To evaluate the serum alanine aminotransferase (ALT) variabilities in nonalcoholic fatty liver disease (NAFLD) and correlate it with hepatocyte apoptosis and oxidative stress parameters. Methods: 24 patients with NAFLD and normal ALT were compared with 26 subjects with NAFLD and elevated ALT. Liver oxidative stress was estimated on the basis of malondialdehyde, superoxide dismutase and glutathione. Immunohistochemistry was performed for activated caspase 3 and 8, nuclear factor-κB, antiapoptotic Bcl-2 protein and serum TNF receptor levels were measured. Results: The mean caspase 3 and 8 activity scores, oxidative stress parameters, necroinflammatory grade and prevalence of severe fibrosis were comparable across the groups with normal versus elevated ALT. Patients with nonalcoholic steatohepatitis had significantly higher caspase 3 and 8 activity (percentage of cells with positive staining per high power field), and serum malondialdehyde (mmol/l) levels than those with simple steatosis. ALT elevation was not a risk factor for advanced necroinflammatory grade and fibrosis. A receiver operating characteristic curve did not demonstrate sensitivity and specificity for discriminative power of ALT. Conclusion: Apoptosis and oxidative stress are the main processes contributing to disease progression in NAFLD. ALT values do not correlate with the parameters of apoptosis and oxidative stress. The disease severity can only be determined by liver biopsy.

Treatment of chronic hepatitis B (CHB) is difficult. The response rate to interferon (IFN) as well as nucleoside analogs is not more than 30% in general. While interferon has many side effects, development of resistance in most of the nucleoside analogs precludes long-term use. Both groups of drugs are most efficacious in patients who already had or develop strong cellular immunity with treatment. A pre-S2-containing vaccine was shown to enhance cellular immunity and suppress hepatitis B virus (HBV)-DNA in subjects with chronic hepatitis B. We aimed to test the efficacy of short-term use of a nucleoside analog in combination with a pre-S2-containing vaccine in patients with CHB. In this open study, 48 consecutive patients (32 males and 16 females, mean age +/- SD: 33 +/- 12 years) with CHB without cirrhosis were treated with 100 mg/day lamivudine and four weekly intramuscular injections of Genhevac B 20 mcg (six doses) for 24 weeks. While 19 patients were hepatitis B e antigen (HBeAg) positive (+ve), 29 patients were Anti-HBe/HBV-DNA +ve at the outset. Response was defined as seroconversion to anti-HBe in HBeAg +ve subjects and normalization of alanine aminotransferase (ALT) with loss of HBV-DNA in anti-HBe/HBV-DNA +ve subjects. HBeAg seroconversion occurred in 5/19 subjects (26%). Eighteen of 29 anti-HBe/HBV-DNA +ves responded. In the follow-up, while relapse was not observed in any of the patients who seroconverted, 11/18 from the anti-HBe/HBV-DNA +ve group relapsed, resulting in a sustained response (SR) rate of 24% in this group. All the relapses happened in the first 48 weeks of follow-up, with no relapse thereafter. Pretreatment high serum HBV-DNA was a strong negative predictor of sustained response (SR) in HBeAg +ve group. Pretreatment serum ALT over 2 x upper limit of normal and HBV-DNA less than 200 pg/ml appeared positive predictors. None of HBeAg +ve previous interferon failures responded. Twenty-four weeks of lamivudine and hepatitis B vaccine treatment induces SR in around 1/4 of the patients with CHB. Most of the responders had high ALT and relatively low DNA.

There is controversial data in the literature about the characteristics or features of dual hepatitis B and C infection. Several studies have reported that the dual infection has a more severe histological picture; faster progression leading to cirrhosis and a higher risk for hepatocellular carcinoma compared with the single infections. These findings have not yet been supported. We assessed the patients with dual hepatitis B and C infection with respect to their different features in our country. Method: the chronic hepatitis patients of our clinics were tested, and both HBsAg and anti-HCV positive patients with chronic hepatitis were enrolled to the study. All patients were tested for the biochemical parameters and the presence of HBV-DNA and HCV-RNA. Results: Of the 1950 patients, 51 (2.6%) were both HBsAg and anti-HCV positive and 67 were antidelta positive. Patients were followed up for 5.4 ± 2.1 years. Of the 51 dual hepatitis patients, 6 had no HBV-DNA and HCV-RNA detectable by PCR, 36 were only HCV-RNA positive, 9 were only HBV-DNA positive and 3 were both HBV-DNA and HCV-RNA positive. Dominant infection in ¾ of the patients was hepatitis C. Clinical and histological properties of the cases with dual Hepatitis B and C infection showed no significant differences compared to the single infections. In conclusion, regarding the prognosis, no significant differences were found between such dual and single infections. Dual infection with hepatitis B virus and delta virus is a significantly more severe condition than the dual infection with hepatitis B and C viruses.

Background and aim Delta hepatitis is characterized by rapidly progressive liver disease with adverse prognosis in most patients. Patients benefit from high doses and prolonged courses of interferon (IFN) therapy; however, lamivudine as a single agent has been disappointing. Data relating to the efficacy of IFN and lamivudine in combination is limited. The aim of this study was to test the efficacy of IFN-alpha 2b and lamivudine combination treatment in comparison to IFN-alpha 2b alone in patients with chronic delta hepatitis. Methods Twenty-six patients with chronic delta hepatitis were randomized into two groups. Twelve patients received IFN-alpha 2b alone (eight men, four women; mean +/- SD age: 43.83 +/- 8.57 years), and 14 patients received IFN-alpha 2b plus lamivudine combination (seven men, seven women; mean +/- SD age: 42.5 +/- 11.02 years). The dose of IFN-alpha 2b was 10 MU t.i.w. and of lamivudine was 100 mg/day. The groups were comparable in reference to serum alanine aminotransferase (ALT), aspartate aminotransferase, bilirubin, albumin levels, histological activity and stage. Four patients (33.3%) in the IFN group and two (14.3%) in the combination group had cirrhosis (P = 0.2). The duration of treatment was 48 weeks with an untreated follow-up period of at least 96 weeks (mean +/- SD, 3.1 +/- 1.9 years). A liver biopsy was performed at the end of treatment. Results Eight patients from the IFN group and 11 from the combination group completed treatment. Serum ALT values became normal in 8/14 patients (57.1%) treated with IFN plus lamivudine and in 5/12 patients (41.7%) treated with IFN alone (P = 0.43). Serum hepatitis delta virus RNA was no longer detectable in nine of 14 (64.3%) patients treated with IFN plus lamivudine as compared to five of 12 (41.6%) patients treated with IFN alone (P = 0.024). In both groups female patients had significantly better virological response rate (P = 0.007). There was a significant improvement in histological activity in the combination group (mean decrease 5.27 +/- 1.08 score, P = 0.001), but not in the IFN group (mean decrease 1.44 +/- 1.59 score, P = 0.39). No significant improvement was observed in regards to fibrosis. Four of the 14 patients (28.6%) treated with combination therapy as compared to two of 12 patients treated with IFN (16.7%) were sustained virological responders (P = 0.47). The 5-year survival rate was 65% in the IFN group and 85% in the combination group (P > 0.05). Conclusion Interferon and lamivudine in combination is an encouraging treatment method and may be superior to IFN alone in chronic delta hepatitis.

Carbamazepine is used to control seizures. Its common side effects are sleep disorders, anorexia, nausea, vomiting, polydipsia, irritability, ataxia, and diplopia. Involvement of the immune system is rare, and few cases of decreased immunoglobulin levels have been reported. We describe a patient with low immunoglobulin levels due to carbamazepine use who presented with recurrent urinary tract infection. Intravenous immunoglobulin was administered, and immunoglobulin levels increased to safer levels after discontinuation of carbamazepine. Previous reports describe severe infection after carbamazepine-induced hypogammaglobulinemia. Therefore, in patients using antiepileptics, particularly carbamazepine, serum immunoglobulin levels should be checked in those with recurrent infections. (C) 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

A letter in response to: Yilmaz Y, Kurt R, Kalayci C. Apoptosis in nonalcoholic steatohepatitis with normal aminotransferase values: zooming in on cytokeratin 18 fragments. Biomarkers Med. 4(5), 743–745 (2010).

Fatty liver is a common disease in developed countries. We investigated the frequency of operation in patients with fatty liver and the frequency of cancer in their first-degree relatives.In this study, we evaluated 105 patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD), 121 patients with hepatitis C (61 patients with fatty liver and 60 patients without fatty liver), 50 patients with inflammatory bowel disease (IBD), and 109 patients with dyspepsia as a control group.There was no difference for sex, mean age, and marital status among the groups, except that patients with IBD were younger than others (p 0.001). The frequency of cancer in family was as follows: 18 % in IBD, 9 % in dyspepsia, 28 % in hepatitis C with hepatic steatosis, 21.5 % in hepatitis C without steatosis, and 27 % in NAFLD (p = 0.006). Then, we divided the study group into two groups-group 1: IBD + dyspepsia + hepatitis C without hepatic steatosis, and group 2: hepatitis C with hepatic steatosis + NAFLD-and performed the same analysis. We found that the frequency of cancer in family was 16 % in group 1 (the patients without fatty liver) vs. 24.4 % in group 2 (those with fatty liver; p = 0.037). We also investigated the rate of operation in patients. The results were as follows: 33 % in group 1 vs. 43 % in group 2 (p = 0.043).Independently of the underlying chronic diseases, occurrence of fat in the liver increased the frequency of operation in patients with fatty liver and the rate of cancer in their first-degree relatives. Understanding the underlying causes of fatty liver forms might decrease the cancer frequency in the population and number of operation in patients with fatty liver.

Several studies have reported that interferon therapy increases elimination rate of HBeAg and anti-HBe seroconversion in chronic hepatitis B (CHB) patients. We aimed to evaluate long-term results of interferon-α treatment in HBeAg positive CHB patients in a country with exclusively D genotype. Seventy-one naive CHB patients (M/F 61/10, mean age 29 ± 12 years, range 16–62) treated with 6 months of interferon-α 2b, 10 MU tiw and had a consequent untreated follow-up period of at least 10 years with positive response were identified and their data were reviewed. The therapy response was defined as HBeAg seroconversion with undetectable HBV-DNA. The responders were followed-up at 3–6-month intervals. Twenty-eight (39%) patients achieved HBeAg seroconversion (25 within the therapy, 3 within the consequent 12 months off-treatment follow-up). The responders were followed-up with a mean period of 152 months (range 123–181). In the follow-up period, 21/25 (84%) initial responders relapsed. On the other hand, 3 patients who did not respond at the end of therapy sustained the response during follow-up. Hence 21/28 total responders relapsed (75%), either with HBeAg reversion (3, 14.3%) or HBV-DNA elevation over 2000 IU/ml (or its equivalent in other types of definitions) and ALT elevation (18, 85.7%). The sustained response was present in 7 patients (9.8%). Serious side effects precluding completion of treatment occurred in three patients (4.2%). In multivariate analysis none of the pre-treatment parameters appeared to be significant in predicting response. Sustained response to interferon treatment is low in HBeAg positive CHB patients with genotype D.

Hepatocyte apoptosis is an important and invasive predictor of liver injury and fibrosis in non-alcoholic fatty liver disease (NAFLD). Increased gamma-glutamyltranspeptidase (GGT) level is frequently observed in NAFLD. Hepatocyte growth factor (HGF) stimulates fibrogenesis and is correlated with GGT. The study aimed to determine whether GGT can distinguish NAFLD patients at high risk.Fifty biopsy-proven NAFLD patients (M/F: 24/26) were divided as the normal GGT group (n = 25) and the high GGT group (n = 25) (each patients' GGTtwo fold of upper-limit of normal). Liver histology was graded according to Brunt et al. TNF-sRp55, caspase-3 and 8, NFkappaB and Bcl-2 were measured by immunohistochemical methods. For statistical analysis, Student's t test, chi-square test, multivariate regression analysis and the area under receiver operating characteristic (ROC) curve were used.The high GGT group had significantly higher NFkappaB, caspase-3 and 8, and Bcl-2 levels (54.52 +/- 26.02, p = 0.002; 55.95 +/- 27.18, p = 0.002; 47.85 +/- 28.04, p = 0.001; 11.19 +/- 12.33, p = 0.016, respectively). Serum TNF-sRp55 levels of both groups were similar (2922.93 +/- 307.26, and 2885 +/- 194.47; p = 0.78). Differences in reference to histological steatosis grade and inflammation were not significant. However, fibrosis stage was higher in the high GGT group (p = 0.048).Multinominal logistic regression analysis showed that increased GGT level was a risk factor for advanced fibrosis in NAFLD (OR: 1.0, CI: 0.98-1.01; p =0.032). Using serum GGT levels the area under the ROC curve for the prediction of advanced fibrosis was 0.74 (95% CI: 0.54-0.94). The serum GGT cut-off value for the prediction of advanced fibrosis was 96.5 U/L; with 83% sensitivity and 69% specificity.

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition associated with obesity and insulin resistance (IR). Leptin plays a key role in the control of energy balance, and insulin sensitivity. In this study, we aimed to examine whether serum leptin levels correlate with insulin resistance, oxidative stress parameters and the severity of histological changes in NAFLD. Methods: Fifty-two patients (M/F: 28/24) with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied. Serum leptin levels were measured by radioimmunoassay. HOMA (homeostasis model assessment) IR index was calculated. Comparisons between the patients with NAFLD and non-alcoholic steatohepatitis (NASH) were performed using the Student’s t test. Multivariate regression analysis and the area under the receiver operating characteristic (ROC) curve were used to identify the independent predictors for NASH. Results: We found no association between serum leptin, fasting insulin levels, and oxidative stress parameters. ROC curve and multiple regression analysis revealed no association between the severity of histological changes and serum leptin levels. During six months followed-up period only NASH group with elevated leptin levels had significant reductions of ALT and AST values (p = 0.03, and 0.005, respectively). Conclusion: Our findings show a preventive effect of leptin against progressive liver injury in NAFLD.

Hepatitis C virus (HCV) infection is endemic among hemodialysis (HD) patients. It is well known that HCV causes approximately 50% of hepatosteatosis in patients with normal renal function and that this rate is higher in patients infected with genotype 3. The aim of this study was to investigate the rate of steatosis, the regression in steatosis with interferon (IFN) treatment and factors affecting IFN treatment in hemodialysis patients with chronic hepatitis C (CHC).Thirty-seven HD patients with CHC were included in the study. All patients received hemodialysis treatment three times a week during the follow-up period. Patients were treated with 3 million units (MU) of IFN-alpha 2a monotherapy for at least 6 months. All patients were evaluated by liver biopsy before therapy and 16 were evaluated at 12-month follow-up.Mean age of the 37 patients (23 M, 14 F) was 44+/-11.6 years and body mass index was 21.8+/-1.8 kg/m2. Twenty-eight of the patients included in the study (75.7%) were of genotype 1b. RNA response after treatment was 78.4% and sustained response after the follow-up period of 14.9+/-8 months was 54%. Total cholesterol values were directly proportional to RNA response (p0.003) and inversely correlated with resistance to treatment (p0.008). Triglyceride values were inversely correlated with resistance to treatment (p0.041). At evaluation of steatosis scores in baseline liver biopsy, severe and mild to moderate steatosis was found in 3 (8.1%) and 16 (43.2%) patients, respectively. In 18 patients (48.7%) there was no steatosis. The rate of steatosis was found to be 44% in control biopsies. While there was no regression in the rates of steatosis (p=0.499), it was found that steatosis regressed after IFN treatment in two patients infected with genotype 3. No correlations were observed between HCV genotype, sustained response and liver steatosis.Response and sustained response rates of HD patients with HCV in a Turkish population were found to be high after IFN monotherapy. With the exception of two patients infected with genotype 3a, the rate of liver steatosis was found to be high and did not change after IFN treatment in HD patients with CHC.

Increased deposition of the extracellular matrix components, particularly collagen, is a central phenomenon in liver fibrosis. Stellate cells, the central mediators in the pathogenesis of fibrosis are activated by free radicals, and synthesize collagen. Melatonin is a potent physiological scavenger of hydroxyl radicals. Melatonin has also been shown to be involved in the inhibitory regulation of collagen content in tissues. At present, no effective treatment of liver fibrosis is available for clinical use. We aimed to test the effects of melatonin on dimethylnitrosamine (DMN)-induced liver damage in rats. Wistar albino rats were injected with DMN intraperitoneally. Following a single dose of 40 mg/kg DMN, either saline (DMN) or 100 mg/kg daily melatonin was administered for 14 days. In other rats, physiologic saline or melatonin were injected for 14 days, following a single injection of saline as control. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) levels were evaluated in blood and tissue homogenates. DMN caused hepatic fibrotic changes, whereas melatonin suppressed these changes in five of 14 rats (P < 0.05). DMN administration resulted in increased hydroxyproline and MDA levels, and decreased GSH and SOD levels, whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice.

model. This predictive model (PPV 79% and NPV 80%) did not perform substantially better than the three other equations and did not outperform ultrasound for excluding NAFLD (NPV 82%). Conclusions: Freely available prediction rules and the tested novel biomarkers have insufficient diagnostic accuracy for diagnosing or excluding NAFLD in severely obese children. Ultrasound remains the most suitable tool to exclude NAFLD in daily routine in this group. Table 1. Diagnostic performance of non-invasive prediction rules and ultrasound.

G A A b st ra ct s of uniform uptake within the DC compared with the irregular uptake in the AC. 3. No subject was identified as having zero uptake in any segment by all observers. 4. The quantitative analysis of uptake also showed differences in the percentage uptake for the various segments, highest in C+AC. Discussion 1. The pattern of uptake, irregular in C+AC and more uniform elsewhere, probably explains the differences between quantitative and qualitative results. 2. These findings confirm our anecdotal observation but do not explain the underlying mechanisms. 3. Possible reasons for our findings include water reabsorption, colonic muscle uptake and uptake by microbes when fermenting undigested fibre. Conclusion FDG uptake in the colon occurs frequently and offers the potential for a non-invasive probe of colonic physiology. Quantitative uptake (mean ± SD) in 9 patients (1 excluded because of anomalously high uptake in DC)

Apoptosis and oxidative injury are recognized as the most important causes of hepatocyte injury in non-alcoholic fatty liver disease (NAFLD). We aimed to search for the association between serum alanine aminotransferase (ALT) levels and hepatocyte apoptosis and oxidative stress parameters in NAFLD. Fifty patients (24 male / 26 female, mean age: 47.3 ± 10.1 years) with biopsy-proven NAFLD were studied. While ALT was in normal range in 24 subjects, it was elevated in 26. Upper range of normal was set to 19 U/L for women and 30 U/L for men. While non-alcoholic fatty liver (NAFL) denotes simple steatosis, nonalcoholic steatohepatitis (NASH) denotes the presence of inflammation, ballooned hepatocytes and fibrosis. Liver oxidative stress was estimated on the basis of tissue gluthathione concentration, and superoxide dismutase (SOD), and malondialdehyde (MDA) activities in tissue and serum specimens. Immunohistochemistry was performed for activated caspase 3 and 8, nuclear factor kB (NF-kB), antiapoptotic Bcl-2 protein, and tumor necrosis factor receptor (TNF-sRp55). The mean caspase 3 and 8 activity scores, oxidative stress parameters, mean necroinflammatory grade and prevalence of severe fibrosis were comparable across the groups with normal versus elevated ALT. Only patients with NASH had significantly higher caspase 3 and 8 activity, and serum MDA levels than those with NAFL (54.81±18.06, 39.81±27.43, p=0.04; 49.62±17.66, 26.17±15.03, p=0.03, and 5.09±0.77, 3.58±0.50, p= 0.049, respectively). Multiple regression analysis revealed that ALT elevation was not a risk factor for advanced necroinflammatory grade and fibrosis (OR:0.99, p=0.74, CI: 0.991.00, and OR:0.99, p=0.71, CI:0.98-1.00, respectively). Area under the receiver operating characteristic curve (AUROC) did not show any significant sensitivity and specificity for discriminative power of ALT (according to the upper limits above) for the necroinflammatory and fibrosis severity (AUROC 0.49; 95 % CI: 0.57-0.91, and AUROC 0.43; 95 % CI: 0.190.67, and respectively). In conclusion, we demonstrated that apoptosis and oxidative stress are the main events contributing to disease progression in NAFLD and serum ALT values do not correlate well with the parameters of these injurious processes or the severity of resultant histological changes.

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.