Predicting fibrosis progression in non-alcoholic fatty liver disease patients using the FAST Score: A paired biopsy study.

Background and Aim: This study aimed to investigate the predictive value of various non-invasive scores for identifying the progression of hepatic fibrosis over time in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). Materials and Methods: We examined 69 patients with NAFLD who had undergone two liver biopsies at an average interval of 21.3±9.7 months. Progression and regression of fibrosis were defined as an increase or decrease of at least one stage in fibrosis between the initial and follow-up biopsies, respectively. The Fibrosis-4 Index (FIB-4), NAFLD Fibrosis Score (NFS), Agile 3+, Agile 4, and FibroScan-AST (FAST) scores were calculated at the initial biopsy. Results: Comparison of paired biopsies revealed that 45% of participants (n=31) exhibited no change in fibrosis stages, 26% (n=18) experienced progression, and 29% (n=20) demonstrated regression. Multivariable logistic regression analysis identified the FAST score as the only independent predictor of progressive fibrosis, with the odds increasing by 19% (95% CI: 8-38%, p<0.05) for each unit increase in the FAST score at the initial biopsy. No independent predictors for fibrosis regression were identified. Conclusion: Higher baseline FAST scores were associated with an increased likelihood of fibrosis progression, independent of other variables. Thus, the FAST score could serve as both a diagnostic and prognostic tool for fibrosis in patients with NAFLD.

Prognostic significance of metastatic lymph node ratio in gastric cancer: a Western-center analysis.

BACKGROUND: Tumor-node-metastasis (TNM) staging is the central gastric cancer (GC) staging system, but it has some disadvantages. However, the lymph node ratio (LNR) can be used regardless of the type of lymphadenectomy and is considered an important prognostic factor. This study aimed to evaluate the relationship between LNR and survival in patients who underwent curative GC surgery. METHODS: All patients who underwent radical gastric surgery between January 2014 and June 2022 were retrospectively evaluated. Clinicopathological features of tumors, TNM stage, and survival rates were analyzed. LNR was defined as the ratio between metastatic lymph nodes and total lymph nodes removed. The LNR groups were classified as follows: LNR0 = 0, 0.01 < LNR1 ≤ 0.1, 0.1 < LNR2 ≤ 0.25 and LNR3 > 0.25. Tumor characteristics and overall survival (OS) of the patients were compared between LNR groups. RESULTS: After exclusion, 333 patients were analyzed. The mean age was 62 ± 14 years. According to the LNR classification, no difference was found between groups regarding age and sex. However, TNM stage III disease was significantly more common in LNR3 patients. Most patients (43.2%, n = 144) were in the LNR3 group. In terms of tumor characteristics (lymphatic, vascular, and perineural invasion), the LNR3 group had significantly poorer prognostic factors. The Cox regression model defined LNR3, TNM stage II-III disease, and advanced age as independent risk factors for survival. Patients with LNR3 demonstrated the lowest 5-year OS rate (35.7%) (estimated mean survival was 30 ± 1.9 months) compared to LNR 0-1-2. CONCLUSION: Our study showed that a high LNR was significantly associated with poor OS in patients who underwent curative gastrectomy. LNR can be used as an independent prognostic predictor in GC patients.

Evaluation of mucosal status in the follow-up of pediatric patients with celiac disease: the role of serology.

Recent guidelines suggest non-biopsy serology-based approach for the diagnosis of celiac disease; however, there is no evidence-based data regarding noninvasive follow-up of mucosal healing. The aim of this study is to investigate the efficacy of serology in reflecting mucosal status in the follow-up of pediatric patients with celiac disease. This is a validation study conducted at a university hospital. Patients who had biopsy proven celiac disease (Marsh III) at diagnosis, and had been followed-up for at least 12 months, were prospectively evaluated with duodenal biopsies. tTG-IgA and EMA tests were performed on the day of endoscopy. One hundred four patients with a mean age of 7.4 ± 4.02 years were included in the study. The sensitivity and specificity of tTG-IgA were 85.2% and 61% respectively, with a high negative predictive value (NPV) of 92.2% but a very low positive predictive value (PPV) of 43.4%. We found that a cutoff value of 68.5 U/mL for tTG-IgA had a sensitivity, specificity of 85.2% and 85.7% respectively. The AUC was 0.891. The sensitivity and specificity of EMA was 77.8% and 87% respectively, with a high NPV of 91.8% but low PPV of 67.7%. CONCLUSION: This study suggests that negative tTG-IgA and/or EMA can be used as an indicator of mucosal improvement in the follow-up of pediatric patients with celiac disease. However, positive serology (i.e., < 10 × ULN) may be misleading in reflecting mucosal status in the follow-up of pediatric patients with celiac disease. WHAT IS KNOWN: • The tissue transglutaminase IgA (tTG-IgA) and endomysium IgA (EMA) tests are widely used, sensitive and reliable diagnostic tests, but their role in monitoring adherence to dietary treatment in celiac patients has not yet been demonstrated. • There is still no reliable and non-invasive marker of persistent villous atrophy or mucosal recovery. WHAT IS NEW: • Negative celiac serology detected in the follow-up of pediatric patients with celiac disease was successful in demonstrating histopathological mucosal healing. • Positive celiac serology, which is highly reliable in the diagnosis of celiac disease, has not been successful in reflecting mucosal status when used in the follow-up of pediatric patients with celiac disease.

The Contribution of Additional Sampling in Cholecystectomy Materials: A Multicenter Prospective Study.

OBJECTIVE: Cholecystectomy materials are frequently encountered in routine practice. The aim of this study was to determine the true frequency of gallbladder lesions, the diagnostic consistency, and standardization of reports after macroscopic sampling and microscopic evaluation based on previously defined criteria. MATERIAL AND METHOD: 14 institutions participated in the study within the Hepato-Pancreato-Biliary Pathology Study Group. Routinely examined cholecystectomies within the last year were included in the study in these institutions. Additional sampling was performed according to the indications and criteria. The number of blocks and samples taken in the first macroscopic examination and the number of blocks and samples taken in the additional sampling were determined and the rate of diagnostic contribution of the additional examination was determined. RESULTS: A total of 5,244 cholecystectomy materials from 14 institutions were included in the study. Additional sampling was found to be necessary in 576 cases (10.98%) from all institutions. In the first macroscopic sampling, the mean of the numbers of samples was approximately 4 and the number of blocks was 2. The mean of the numbers of additional samples and blocks was approximately 8 and 4, respectively. The diagnosis was changed in 144 of the 576 new sampled cases while the remaining 432 stayed unaltered. CONCLUSION: In this study, it was observed that new sampling after the first microscopic examination of cholecystectomy materials contributed to the diagnosis. It was also shown that the necessity of having standard criteria for macroscopic and microscopic examination plays an important role in making the correct diagnosis.

Change in standardized uptake values in delayed 18F-FDG positron emission tomography images in hepatocellular carcinoma.

Delayed 18F-2-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography (PET) imaging has been associated with improved diagnostic yield in several malignancies; however, data on the use of delayed imaging in patients with hepatocellular carcinoma (HCC) is scarce. This study aimed to examine tumoral and background standardized uptake value (SUV) alterations in dual-phase F-FDG PET/computed tomography (CT) imaging.Fifty-two HCC cases underwent dual-time-point F-FDG PET/CT examination where early and delayed images were obtained. The maximum and mean SUVs (SUVmax and SUVmean) of the tumor were determined for both time points. Similarly, the average SUVmean were also determined for background (liver, soft tissue, and spleen). Changes in tumoral and background SUV between early and delayed images were examined.The mean age was 62.0 ±â€Š12.9 years (range, 20-88 years) and the majority of the patients were men (86.5%). Tumor SUVs, both tumor SUVmean and tumor SUVmax, significantly increased at delayed images when compared to early images. In contrast, the average SUVmean for the liver, soft tissue, and spleen significantly decreased at delayed images.A significant increase in tumor SUV in delayed images in contrast to a significant decrease in background SUVs suggests that delayed images in HCC may contribute to diagnostic performance through a potential increase in the contrast between the tumor and background. However, further studies with larger sample sizes including patients with benign lesions and different grades of the disease are warranted to better elucidate the diagnostic contribution as well as the association of delayed imaging values with prognosis.

A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods: A Multicentre Study.

OBJECTIVE: As there is continuing disagreement among the observers on the differential diagnosis between the epithelial changes/lesions and neoplasms of the gallbladder, this multicentre study was planned in order to assess the rate of the epithelial gallbladder lesions in Turkey and to propose microscopy and macroscopy protocols. MATERIAL AND METHOD: With the participation of 22 institutions around Turkey that were included in the Hepato-Pancreato-Biliary Study Group, 89,324 cholecystectomy specimens sampled from 2003 to 2016 were retrospectively evaluated. The numbers of adenocarcinomas, dysplasias, intracholecystic neoplasms/adenomas, intestinal metaplasias and reactive atypia were identified with the review of pathology reports and the regional and countrywide incidence rates were presented in percentages. RESULTS: Epithelial changes/lesions were reported in 6% of cholecystectomy materials. Of these epithelial lesions, 7% were reported as adenocarcinoma, 0.9% as high-grade dysplasia, 4% as low-grade dysplasia, 7.8% as reactive/regenerative atypia, 1.7% as neoplastic polyp, and 15.6% as intestinal metaplasia. The remaining lesions (63%) primarily included non-neoplastic polypoids/hyperplastic lesions and antral/pyloric metaplasia. There were also differences between pathology laboratories. CONCLUSION: The major causes of the difference in reporting these epithelial changes/lesions and neoplasms include the differences related to the institute's oncological surgery frequency, sampling protocols, geographical dissimilarities, and differences in the diagnoses/interpretations of the pathologists. It seems that the diagnosis may change if new sections are taken from the specimen when any epithelial abnormality is seen during microscopic examination of the cholecystectomy materials.

Helicobacter pylori is undetectable in intraductal papillary mucinous neoplasm.

BACKGROUND: About half of the world population is infected with Helicobacter pylori (H. pylori), a bacterium associated with gastric cancer and considered to be a risk factor for pancreatic ductal adenocarcinoma. Whether the bacterium is associated with intraductal papillary mucinous neoplasm, believed to be a precursor of pancreatic ductal adenocarcinoma, is unknown. The aim of this study was to investigate the presence of H. pylori DNA in tissue sections of intraductal papillary mucinous neoplasm. METHODS: The presence of H. pylori DNA was tested in a retrospective controlled study of formalin-fixed, paraffin-embedded pancreatic tissues from 24 patients who underwent surgery for intraductal papillary mucinous neoplasm. Histologically normal tissues surrounding neoplasms were used as control. H. pylori DNA was evaluated after deparaffinization, DNA extraction, and purification, and results were evaluated statistically. RESULTS: Samples were collected from 13 males and 11 females with mean age 59 years (range 44-77), and consisted of 19 cases of main-duct and three cases of branched-duct intraductal papillary mucinous neoplasm. Two patients were diagnosed with pancreatic cancer and main-duct intraductal papillary mucinous neoplasm. H. pylori DNA was not detected either in intraductal papillary mucinous neoplasm tissue, or in surrounding normal tissue. CONCLUSIONS: Although H. pylori has been implicated in pancreatic ductal adenocarcinoma, it may not play a key role in the development of intraductal papillary mucinous neoplasm.

Nonalcoholic Fatty Liver Disease is Associated with Erectile Dysfunction: A Prospective Pilot Study.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Although the link between MetS and erectile dysfunction (ED) is well known, clinical studies investigating the association between NAFLD and ED are scant. AIM: To evaluate the relationship between NAFLD and ED. METHODS: Male patients with biopsy-proven NAFLD were prospectively asked to fill the five-item International Index of Erectile Function (IIEF-5) questionnaire. Their clinical and histologic variables were compared with the IEFF scores. MAIN OUTCOME MEASURES: IIEF scores; proportions of NAFLD patients who demonstrated ED and/or MetS; association between the severity of histological hepatic damage and ED. RESULTS: Forty male patients having an age range of 33 (24-57) and a mean age of 40.13 ± 10.22 years with biopsy-proven NAFLD had a median IIEF-5 score of 16 (9-25) and MetS was present in 23 (57.5%). ED severity distributions as moderate, mild, and no ED were 11 (27.5%), 16 (40%), and 13 (32.5 %), respectively. Histological NAFLD score was significantly higher in patients having ED compared with patients with no ED (5.63 ± 1.39 vs. 4.15 ± 1.46; P = .006). MetS diagnosis was significantly more common in patients having ED, compared with those without ED [19 (70.4%) vs. 4 (30.8%), respectively, P = .018)]. When patients with and without ED were compared, gamma glutamyl transferase was significantly lower in ED, whereas components of MetS did not correlate with ED. After multivariate analysis, NAFLD score has remained the only significant outcome associated with ED [P = .03; OR (95% CI): 2.38 (1.079-5.238)]. CONCLUSION: The current clinical study demonstrates a significant association between nonalcoholic steatohepatitis and ED for the first time. Our findings suggest liver damage may play role in the pathogenesis of ED in patients with NAFLD. Future studies are needed to expand the underlying common mechanisms responsible for this novel hypothesis.

HER-2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters.

OBJECTIVE: Human epidermal growth factor-2 (HER-2) overexpression has prognostic value in breast cancer. However, the significance of HER-2 positivity in gastric cancer is controversial. In this study, we investigated the frequency of overexpression of HER-2 and its relationship with clinicopathological findings and impact on survival in gastric cancer. MATERIAL AND METHODS: Gastric cancer patients, operated in Marmara University Faculty of Medicine, Pendik Training and Research Hospital, General Surgery Department, between January 2012-December 2013 were enrolled in this study. Medical records were retrospectively evaluated. Tissue samples were stained by immunohistochemistry (IHC) method, and were followed by fluorescence in situ hybridization (FISH) in those with positive results. HER-2 expression rates and its association with other histopathological features and survival have been analyzed. RESULTS: 135 patients were enrolled in the study, with 88 (65%) male and 47 (35%) female patients. The median age was 61 (29-84) years. Only 11 patients (8%) were positive for HER-2. HER-2 positive patients were similar to negative patients in terms of age, gender, tumor size, tumor location, tumor T stage, lymph node metastasis, histological type, differentiation, lymphovascular invasion, perinodal, perineural invasion and stage. No significant difference was detected on 1 and 2-year overall and disease-free survival rates between receptor positive and negative groups. CONCLUSION: Consistent with the literature data, HER-2 positivity rate in this study was approximately 8%, but this positivity has not been found to be associated with either clinical and pathological parameters or overall and disease-free survival.

Is perineural invasion (PN) a determinant of disease free survival in early stage colorectal cancer?

BACKGROUND/AIMS: The prognostic importance of perineural invasion (PN) in colorectal cancer (CRC) is unclear. The aim of this study to find out whether the PN was an independent stratification factor of postoperative relapse in curatively resected high-risk stage II & III CRC patients who were treated with adjuvant therapy. METHODOLOGY: Data of patients with high risk stage II & all stage III CRCs treated with adjuvant chemotherapy were retrospectively analyzed. Pathological features of final surgical specimen were noted. Disease-free survival was determined by Kaplan-Meier estimator, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test. RESULTS: PN was found to be positive in 26% in the files of 593 eligible patients. In 21% of the reports PN status was not reported. Presence of PN in the resected primary tumors did not have independent effect on DFS. Further analyses for importance of PN on DFS of colon or rectal cancers did not show any effect. CONCLUSIONS: This study had failed to demonstrate any prognostic effect of PN for DFS in surgically resected stage II and III CRC patients who received adjuvant treatments.

Preoperative chemoradiation therapy decreases the number of lymph nodes resected during esophagectomy.

BACKGROUND: This study aimed to analyze the effect of preoperative chemoradiation on the adequacy of lymph node dissection. METHODS: Patients with esophageal cancer treated with esophagectomy by the same surgeon between 2004 and 2011 were reviewed. Specimens were examined by the same pathologist. Patients were grouped into two depending on the type of treatment received. RESULTS: Forty-seven patients with curative esophagectomy were included in the study. Twenty patients had preoperative chemoradiation followed by surgery and 27 had surgery alone. Open and hybrid esophagectomy approaches were used. The average number of lymph nodes dissected was 16 ± 10 (1-39). There was a significant decrease in the number of lymph nodes examined in patients with preoperative chemoradiotherapy in comparison to surgery alone (p = 0.001). Median length of stay was 12 days. R0 resection rate was 96%. The median survival was 36.3 months, with a 42% 5-year survival. Seven patients (25%) had complete pathologic response following chemoradiation. No significant difference was recorded in terms of disease recurrence (p = 0.3). While morbidity was higher in the preoperative therapy group with 30 day mortality of 10%, type of surgical approach does not seem to influence the number of lymph nodes dissected (p = 0.7). CONCLUSIONS: Preoperative chemoradiation decreases the number of harvested lymph nodes following esophagectomy regardless of the surgical technique used. The optimum number of lymph nodes currently recommended to be dissected for accurate nodal staging and survival needs revision in this group of patients.

A comparison of FibroMeter™ NAFLD Score, NAFLD fibrosis score, and transient elastography as noninvasive diagnostic tools for hepatic fibrosis in patients with biopsy-proven non-alcoholic fatty liver disease.

BACKGROUND: Noninvasive markers that purport to distinguish patients with non-alcoholic fatty liver disease (NAFLD) with fibrosis from those without must be evaluated rigorously for their classification accuracy. Herein, we seek to compare the diagnostic performances of three different noninvasive methods (FibroMeter™ NAFLD score, NAFLD Fibrosis score (NFSA), and Transient Elastrography [TE]) for the detection of liver fibrosis in NAFLD patients. METHODS: A total of 88 patients with biopsy-proven NAFLD were included. The Kleiner system was used for grading fibrosis in liver biopsies. The FibroMeter™ NAFLD score was determined using a proprietary algorithm (regression score). The NFSA score was calculated based on age, hyperglycemia, body mass index, platelets, albumin and serum aminotransferase levels. TE was performed using the Fibroscan apparatus. RESULTS: The sensitivities/specificities for the FibroMeter™ NAFLD score, NFSA, and TE for the diagnosis of significant fibrosis (F2 + F3 + F4 fibrosis) were 38.6%/86.4%, 52.3%/88.6%, and 75.0%/93.2%, respectively. The areas under the receiver operating characteristic curves of TE were significantly higher than those of both the FibroMeter™ NAFLD score and NFSA. No significant differences were found between the FibroMeter™ NAFLD score and NFSA for the detection of significant and severe fibrosis, although the diagnostic performance of the FibroMeter™ NAFLD score was higher than that of the NFSA score for cirrhosis. CONCLUSIONS: In summary, TE showed the best diagnostic performance for the noninvasive assessment of liver fibrosis in NAFLD patients. The diagnostic performances of the FibroMeter™ NAFLD score and NFSA did not differ significantly for the detection of both significant and severe fibrosis.

Detection of hepatic steatosis using the controlled attenuation parameter: a comparative study with liver biopsy.

OBJECTIVE: Measurements of controlled attenuation parameter (CAP) with transient elastography (FibroScan®; EcoSens SA, Paris, France) may provide an accurate noninvasive assessment of hepatic steatosis. Herein, we prospectively determined the accuracy of liver fat quantification with CAP values in patients with chronic liver diseases and compare the results with those of histological assessment of steatosis as reference standard. MATERIALS AND METHODS: We enrolled 50 Turkish patients with various forms of chronic liver diseases. All patients underwent both CAP assessment and ultrasonography-guided liver biopsy. RESULTS: On liver biopsy, 16 (32%) patients had S0, 12 (24%) had S1, 9 (18%) had S2, and 13 (26%) had S3. The CAP values increased significantly (p<0.001) for each steatosis stage on liver biopsy: S0, 222 dB/m; S1, 250 dB/m; S2, 270 dB/m; and S3, 318 dB/m. A cutoff value of 257 dB/m could distinguish significant steatosis (S2-S3) from S0 (Sn 89%, Sp 83%, positive likelihood ratio 5.33, negative likelihood ratio 0.13, AUROC=0.93). Multivariable analysis indicated that neither liver fibrosis (p=0.58) nor disease etiology (p=0.96) had a significant impact on the association between CAP and the stage of steatosis. CONCLUSION: The determination of CAP using transient elastography can represent an important step forward toward the goal of an "imaging liver biopsy".

Atypical presentation of cat-scratch disease in an immunocompetent child with serological and pathological evidence.

Typical cat-scratch disease (CSD) is characterized by local lymphadenopathy following the scratch or bite from a cat or kitten. An atypical presentation which includes liver and/or spleen lesions is rarely reported in an immunocompetent child. Systemic CSD may mimic more serious disorders like malignancy or tuberculosis. Although a diagnosis is difficult to establish in systemic CSD, an early diagnosis and an appropriate treatment are important to prevent complications. Bartonella henselae is difficult to culture, and culture is not routinely recommended. Clinical, serological, radiological, and pathological findings are used for the diagnosis of CSD. Herein we present a case of systemic CSD presenting with hepatic mass in an immunocompetent child. The differential diagnosis is made by serological and pathological evidence. He was successfully treated with gentamicin (7.5 mg/kg) and rifampin (15 mg/kg) for six weeks.

What is the diagnostic utility of endoscopic scoring systems in children?

BACKGROUND/AIMS: The aim of this study was to evaluate the consistency of the Savary-Miller, the Hetzel-Dent and the Los Angeles endoscopic classification systems and to compare them with the esophageal histopathology in children. MATERIAL AND METHODS: Children between the ages of 5-17 years who underwent esophagogastroduodenoscopy were included in the study. The endoscopic reports and the still images of the esophagus were reclassified by the same gastroenterologist according to the Savary-Miller, Hetzel- Dent and Los Angeles scoring systems. The esophageal biopsies were also reevaluated by the same pathologist and the consistency between endoscopic and histopathologic esophagitis was evaluated. RESULTS: A total of 113 out of 192 pediatric patients were included in the study. Seventy-three patients (64.6%) had esophagitis according to the Hetzel-Dent classification, whereas only 20 (17.7%) patients were defined as having esophagitis according to the other two classification systems. The consistency between the Savary-Miller and Los Angeles classifications was excellent (κ: 0.92) but the agreement between the Hetzel-Dent and Savary-Miller and between the Hetzel-Dent and Los Angeles classifications were poor. A total of 82 patients (72.6%) had histopathological esophagitis, and there was a weak consistency between all 3 endoscopic scoring systems and the histopathology. CONCLUSIONS: Since pediatric patients have milder esophagitis than in adults, the use of endoscopic scoring systems developed for adults seems to be inapplicable for children. The inclusion of minimal endoscopic changes in endoscopic scoring systems by using more sensitive and novel endoscopic techniques would increase the sensitivity of these scoring systems in children.

Hepatic expression and serum levels of syndecan 1 (CD138) in patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Syndecan-1 (CD138) is a transmembrane heparan sulfate proteoglycan expressed in the liver which may exert metabolic effects by mediating the hepatic clearance of triglyceride-rich lipoproteins. In the present study, we assayed serum levels and the hepatic expression of syndecan-1 and examined their association with clinical, biochemical, and histologic phenotypes in patients with histology-proven nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 59 patients with biopsy-proven NAFLD and 54 matched controls were enrolled. The analysis of syndecan-1 expression in liver biopsies was performed by immunohistochemistry on formalin-fixed, paraffin-embedded samples. Serum syndecan-1 levels were measured by ELISA. RESULTS: NAFLD patients had significantly higher serum syndecan-1 levels [median: 61 ng/mL (interquartile range: 36-97 ng/mL)] than controls [median: 37 ng/mL (interquartile range: 25-59 ng/mL, Mann-Whitney U test, p < 0.001]. However, we did not find any significant association between serum syndecan-1 and the mean syndecan-1 immunohistochemical score (n = 59, r = 0.064, p = 0.63). Interestingly, the syndecan-1 immunohistochemical score was an independent predictor of HDL cholesterol in NAFLD patients (ß = 0.27; t = 1.99, p < 0.05). CONCLUSIONS: Our data suggest that serum syndecan-1 levels are raised in patients with NAFLD. Moreover, the syndecan-1 immunohistochemical score in the liver is independently associated with HDL cholesterol in this group of patients. These pilot results support further investigation of this molecule in metabolic liver diseases.

Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis.

BACKGROUND & AIMS: Preliminary evidence suggests that inhibition of dipeptidyl peptidase (DPP)-IV preserves pancreatic beta cell function in patients with type 2 diabetes (T2D). However, its effects on liver histology in nonalcoholic steatohepatitis (NASH), hepatic complication of diabetes, have not yet been adequately explored. The present open-label, single-arm observational pilot study investigated the effects of one year of treatment with a dipeptidyl peptidase-IV inhibitor, sitagliptin, on liver histology, body mass index (BMI), and laboratory parameters in NASH patients with T2D. PATIENTS AND METHODS: Paired liver biopsies from 15 diabetic patients with NASH (7 males, 8 females; mean age: 49.7 +/- 8.1 years (range: 36-62)) before and after one year of therapy with sitagliptin 100 mg once daily were studied. Clinical and laboratory parameters were recorded. RESULTS: Treatment with sitagliptin resulted in a significant decrease in ballooning (P = 0.014) and NASH scores (P = 0.04), while the reduction in the steatosis score was of borderline statistical significance (P = 0.054). These effects were accompanied by a significant reduction in body mass index, AST, and ALT levels. CONCLUSION: Our study suggests that sitagliptin ameliorates liver enzymes and hepatocyte ballooning in NASH patients with T2D and may have therapeutic implications.

Circulating levels of vascular endothelial growth factor A and its soluble receptor in patients with biopsy-proven nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Vascular endothelial growth factor A (VEGF) is a multifunctional cytokine affecting angiogenesis and vascular function. The biological activity of VEGF is modulated by its soluble receptor VEGFR-1 (sVEGFR-1). We explored the associations of VEGF and sVEGFR-1 concentrations with liver histology in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). METHODS: The study was comprised of 99 patients with NAFLD and 75 healthy controls. Serum VEGF and sVEGFR-1 concentrations were measured using commercially available enzyme-linked immunosorbent assays. RESULTS: Serum VEGF levels did not differ in patients with NAFLD (1882 ± 942 pg/mL) compared with healthy controls (1985 ± 945 pg/mL, p = 0.42). However, compared with healthy subjects, levels of sVEGFR-1 were significantly lower in patients with NAFLD (1.59 ± 0.58 ng/mL vs. 1.16 ± 0.34 ng/mL, respectively, p <0.001). After allowance for potential confounders, serum sVEGFR-1 levels retained their independent significance as a predictor of liver fibrosis in patients with NAFLD (ß = -0.19; t = -1.81, p <0.05). CONCLUSIONS: Our results show that patients with biopsy-proven NAFLD have a significant reduction in serum sVEGFR-1 concentrations that predict the degree of liver fibrosis, independent of potential confounders.

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 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.