The liver-kidney axis: Is serum leptin a potential link in non-alcoholic fatty liver disease-associated chronic kidney disease?

BACKGROUND 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.

The impact of celiac disease and duration of gluten free diet on anterior and posterior ocular structures: Ocular imaging based study.

PURPOSE: To evaluate the eyes of adult celiac disease (CD) patients and investigate the association between these ocular parameters with celiac specific antibodies and duration of gluten free diet (GFD). METHODS: This cross-sectional study included 72 eyes of 36 CD patients (18-51 years of age) and 70 eyes of 35 age- and sex-matched healthy controls. In addition to a complete ophthalmologic examination, all patients were scanned by a Scheimpflug camera, specular microscopy and spectral domain optical coherence tomography. RESULTS: Endothelial cell density (ECD), anterior chamber angle (ACA) degrees, anterior chamber depth (ACD), anterior chamber volume (ACV) and central macular thickness (CMT) values were lower in CD patients as compared with control group (p values = 0.038, 0.024, 0.002, 0.038 and 0.046 respectively). ECD and CMT were lower in celiac patients whom endomysial antibodies (EMA) IgA were positive (p = 0.001, p = 0.042 respectively). Tissue transglutaminase IgA antibody (anti tTG IgA) was weakly positively correlated (p > 0.05) with ACD, and positively (r = 0.319; p < 0.05) correlated with ACV. As the duration of compliance to the diet increased in the celiac group the mean and inferior retinal nerve fiber layer (RNFL) thickness decreased (p = 0.035, p = 0.008 respectively). Mean, inferior and temporal RNFL thicknesses were lower in celiac patients whose duration of GFD was longer than 5 years (p < 0.05). CONCLUSIONS: Decreases in ECD, ACA degree, ACD, ACV and CMT can occur in CD patients. In adult celiac patients; ECD, CMT might be effected in the presence of positive EMA, and ACD, ACV might be effected in the presence of higher anti tTG IgA titer. Adult celiac patients who had longer duration of GFD may have thinner RNFL. RNFL may be thinner in celiac patients who comply with GFD for more than 5 years.

Endoscopic Gastrointestinal Anastomosis Using Lumen-apposing Metal Stent (LAMS) for Benign or Malignant Etiologies: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: Endoscopic gastrointestinal anastomosis using lumen-apposing metal stents (EGAL) is a new technique that is used as an alternative method to bypass benign or malignant strictures. Endoscopists take advantage of 2 bowel loops that are close to each other and place a stent between the lumen of these 2 bowel loops. The authors performed this systematic review and meta-analysis to evaluate the efficacy and safety of this rising procedure. METHODS: Electronic database searches were conducted for full eligible articles that were published from the inception to July 2019 using the EGAL procedure to bypass malignant or benign obstruction or to restore bowel integrity after a gastrointestinal altering surgery. The primary outcome of this meta-analysis was to assess efficacy through technical and clinical success. Secondary outcomes were to assess safety through adverse events and to assess the rate of stent maldeployment and the rate of reintervention during the study period. RESULTS: Eight studies were eligible, providing data on 269 patients who underwent 271 EGAL procedures. The median age was 65 years (interquartile range: 63 to 66) with 46% male individuals. Out of 269 patients, 203 underwent EGALs because of malignant etiology and 66 underwent EGAL for benign etiology. The median duration of follow-up was 114 days (interquartile range: 78 to 121). Technical success rate was 94.1% [95% confidence interval (CI), 91.4%-96.9%]. Clinical success rate was 91.4% (95% CI, 88.1%-94.7%). Adverse events rate was 8.5% (95% CI, 4.7%-12.3%). Stent maldeployment rate was 9.5% (95% CI, 3.5%-15.4%) of the total performed EGALs and the reintervention rate was 6.0% (95% CI, 2.3%-9.8%). CONCLUSION: EGAL procedure has high efficacy and a relatively safe profile and it can be performed in selected patients. Comparison between EGAL and other conventional therapies is difficult because of the lack of randomized trials.

Apoptosis and Disease Severity is Associated with Insulin Resistance in Non-alcoholic Fatty Liver Disease.

BACKGROUNDS AND AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Role of oxidative stress and insulin resistance in disease severity of non-alcoholic fatty liver disease.

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 (ß=1.88, p=0.002), serum SOD (ß=0.57, p=0.006), tissue MDA (ß=0.22, p=0.006), tissue SOD (ß=1.48, p=0.071) and stage (ß=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.

Five-year results of oral antiviral therapy in HBeAg-negative chronic Hepatitis B.

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.

Demographic characteristics of chronic pancreatitis patients in the era of endosonography: Experience of a single tertiary referral center in Turkey.

BACKGROUND/AIMS: There are no clinical data available about chronic pancreatitis (CP) on a series of patients of sufficient number in Turkey. In this study, the etiology and clinical features of CP were evaluated in one center, which is a tertiary referral hospital. MATERIALS AND METHODS: The files of 168 patients who had been diagnosed with CP in our Medical Faculty between October 2007 and May 2013 were retrospectively analyzed. The etiological factors, symptoms, complications, and treatment methods were analyzed. RESULTS: The most common etiological factor was alcohol abuse (39%). The average age±SD was 46±15.2 years, and the male:female ratio was 4.2:1 (it was 2.6:1 for other etiologies except alcohol abuse and 15.5:1 in alcoholic CP patients, p<0.05). The most frequent complication was diabetes mellitus (44%). The smoking rate was significantly higher in CP patients with pancreatic calcification (p<0.05). One-third of the patients received various types of endoscopic treatment. During a mean follow-up period of 42±13 months (range, 6-55), pancreatic cancer was detected in four patients (2.3%). CONCLUSION: In majority of the CP patients, the etiology is alcohol abuse in Turkey. The development of diabetes is the most frequent complication of CP, which is independent of the etiology.

Low lipase levels as an independent marker of pancreatic cancer: a frequently neglected condition in clinical setting.

BACKGROUND/AIMS: Low lipase levels, which may be an indication of low production due to organ failure, are frequently encountered in a clinical setting, but are usually overlooked. This study examined the values of low serum lipase levels and other clinical parameters in the diagnosis of several clinical conditions, such as in pancreatic cancer. MATERIALS AND METHODS: Patients with low lipase levels (≤8 U/L) were included in this retrospective study. Clinical data, including diagnostic category, demographic properties, and biochemical and hematological measurements, including serum lipase levels, were extracted. A multivariate analysis was used to identify the independent predictors of certain diagnostic categories. RESULTS: A total of 198 patients with low lipase levels were included. Among these patients with low lipase levels, 45 (22.7%) were diagnosed with pancreas cancer. Multivariate analysis identified low lipase level as a significant predictor of pancreas cancer (OR 0.70 [%95 CI, 0.52-0.93], p=0.02). For predicting pancreatic cancer, an optimal cut-off value of ≤5.5 U/L for lipase was utilized, which had a sensitivity and specificity of 76% and 37%, respectively. CONCLUSION: Low lipase levels close to zero may be an indication of pancreatic cancer and should not be underestimated in the clinical setting. However, large studies are warranted to delineate the exact diagnostic significance of such low lipase levels.