TASL Practice Guidance on the Clinical Assessment and Management of Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists.

Helicobacter Pylori Colonization Density is an Important Risk Factor for Eradication Therapy.

BACKGROUND AND AIMS: Despite the known risk factors, it is not clear why the same treatment protocol for Helicobacter pylori infection (H. pylori) doesnot show a similar effect in patients with common risk factors. We hypothesized that as the severity of H. pylori - induced gastric mucosa inflammation and density increase, the rate of successful treatment decreases. This study aimed to explore the existence of a possible association between gastric H. pylori colonization density and the efficacy of bismuth-containing quadruple eradication therapy. METHODS: A total of 330 patients with H. pylori positive gastritis were initially included; the diagnosis was based on the histopathological examination. H. pylori colonization density was graded according to the Sydney classification: mild (n=101), moderate (104) and severe (98). H. pylori eradication was determined via the 13C-Urea breath test performed eight weeks after therapy. RESULTS: There was no significant difference in terms of the distributions of age, gender, alcohol consumption, and smoking status among the groups (p>0.05). The successful eradication rates of H. pylori were 87.1%, 78.8%, and 75.5%, respectively, for the mild, moderate, and severe H. pylori colonization groups by per-protocol analysis (p=0.038). The eradication rates of H. pylori were 81.5%, 73.2%, and 67.3% respectively, for the mild, moderate, and severe H. pylori colonization groups by intention-to-treat analysis (p=0.017). CONCLUSIONS: Helicobacter pylori colonization severity might predict the usefulness of eradication therapy in pre-treatment assessment. We recommend the use of more effective therapy regimens for H. pylori eradication in patients with severe densities.

Efficacy of EDDY, ultrasonic activation, XP-endo Finisher and needle irrigation on the removal of mTAP from artificially created grooves in root canals.

This study analysed the effect of needle irrigation (NI), passive ultrasonic irrigation (PUI), EDDY and the use of the XP-endo Finisher (XPF) on the removal of modified triple antibiotic paste (mTAP) from artificially created grooves in root canals. Forty-eight maxillary incisors were prepared up to size 50, with a standard groove on one surface of the root canal wall and filled with mTAP. Re-attached roots were analysed based on the activation techniques applied for 180 s with 5 ml 3% sodium hypochlorite. The results showed that EDDY was more effective at removing mTAP than PUI, XPF and needle irrigation (P < 0.05), whereas XPF and PUI were significantly more effective than needle irrigation. (P < 0.05). No significant difference in mTAP removal was observed between XPF and PUI (P > 0.05). These findings suggest that the removal of mTAP can be more efficiently achieved with EDDY than with XPF, PUI or NI.

Is the choice of anesthesia during gastrointestinal endoscopic procedures a result of anxiety?

BACKGROUND AND STUDY AIMS: Esophagogastroduodenoscopy (EGD) and colonoscopy (CS) are vital endoscopic procedures in the diagnosis and follow-up of gastrointestinal tract diseases. Endoscopic procedures can be performed with or without anesthesia as per patient preferences. These procedures can cause some anxiety in almost all patients, and the degree of anxiety differs for each individual. Thus, we aimed to evaluate the trait and state anxiety levels of the patients and assess the relationship between the preference of anesthesia and anxiety levels. PATIENTS AND METHODS: To investigate this issue, 723 patients who underwent elective endoscopy (EGD and/or CS) were enrolled. The researchers collected sociodemographic data and medical history records as reported by the patients. State and trait anxiety levels of the patients were evaluated using the State and Trait Anxiety Inventory (STAI). RESULTS: The patients were divided into two groups as with anesthesia and without anesthesia. Of the respondents, 43.4% requested anesthesia during endoscopic procedure. Sociodemographic data, except sex, showed similar characteristics. The STAI trait scores of the two groups were similar; however, there was a significant difference in the STAI state scores of the groups (p = 0.018). A significant difference was observed in the anesthesia preference and the type of endoscopic procedure (EGD, CS, or both) (p < 0.001). Type of endoscopic procedure, STAI state scores, and sex were determined as the predictors of the anesthesia choice. CONCLUSION: Endoscopic procedures are known to cause anxiety among many patients. Our findings suggest that the anesthesia preferences of patients are an important factor in preventing these situational concerns. However, this study found that being a woman and undergoing a CS procedure are important factors related to anesthesia preferences. Thus, more detailed assessments on this subject are required.

The prevalence of metabolic-associated fatty liver disease in the Turkish population: A multicenter study.

Background and Aim: The objective of the present study was to investigate the prevalence of metabolic-associated fatty liver disease (MAFLD) in patients with dyspepsia. Materials and Methods: A total of 909 consecutive patients who presented with dyspepsia at 8 tertiary care centers in Turkey between March 2019 and December 2019 were included. Results: The median age was 47 years. Among them, 30.3% of the patients were obese, 18.8% had type 2 diabetes mellitus (T2DM), 35.1% had metabolic syndrome, 84.8% had dyslipidemia, and 23.9% had hypertension. The prevalence of MAFLD was 45.5%. Among the patients with MAFLD, the prevalence of obesity, T2DM, metabolic syndrome, dyslipidemia, and hypertension was 43.3%, 24.9%, 52.5%, 92.3%, and 31.9%, respectively. MAFLD was significantly associated with all of the metabolic comorbidities (p<0.001). The median Fibrosis-4 Index score of the MAFLD patients was 0.88 (range: 0.1-9.5). Of note, 53 patients with hepatic steatosis did not meet the MAFLD criteria. Conclusion: The results of the present study indicated that there was a significantly high prevalence of MAFLD observed in daily clinical practice in Turkey. Early diagnosis and prevention efforts should be implemented to reduce disease progression, and a region-based strategy is recommended.

High-dose dual therapy is effective as first-line treatment for Helicobacter pylori infection.

BACKGROUND/AIMS: Although many regimens, including quadruple, sequential, and concomitant treatment, are used and recommended as first-line or rescue therapies for Helicobacter pylori infection, eradication rates are still below 90% in intention-to-treat analyses. Treatment protocols with substantially high eradication rates and low antibiotic resistance are needed. In this study, we investigated the efficacy of high-dose dual therapy as first-line treatment in a Turkish population. MATERIALS AND METHODS: All patients underwent upper gastrointestinal endoscopy for the initial H. pylori status because of dyspeptic symptoms. All patients received a 14-day, high-dose dual therapy comprising rabeprazole (20 mg t.i.d.) and amoxicillin (1 g t.i.d.) for H. pylori eradication. H. pylori stool antigen tests of eradication were administered to all participants at least 4 weeks after the completion of the treatment. RESULTS: The high-dose dual therapy demonstrated a 91.3% rate of successful eradication of H. pylori infection. Per-protocol success was 94.4% among female patients (n=51) and 89.6% among male patients (n=86); in terms of gender, the differences were not significant (p=0.310). No side effects were observed during the study in any patient. Six other patients did not take adequate doses of the treatment protocol. CONCLUSION: High-dose dual therapy with rabeprazole and amoxicillin was highly effective and well tolerated as a first-line therapy for H. pylori eradication.

Cyclic fatigue resistance of VDW.ROTATE and Reciproc Blue nickel-titanium files at root canal temperature.

Background. This study aimed to compare the VDW.ROTATE instruments with the Reciproc Blue instruments in different kinematics in terms of the cyclic fatigue resistance. Methods. Sixty instruments, 40 VDW.ROTATE and 20 Reciproc Blue instruments, were divided into three groups (n=20): VDW.ROTATE was used in both continuous rotation and reciprocation, and Reciproc Blue was used in reciprocation only. The cyclic fatigue resistance test was carried out in an artificial canal (60°, r=3 mm) at an intracanal temperature of 35±2°C until fracture, and the time to fracture was recorded in seconds. The data were analyzed statistically using Kruskal-Wallis and Tamhane's T2 tests (P<0.05). Results. DAll the reciprocating motion groups resulted in a longer mean duration to failure than the continuous rotation motion group (P<0.05). Conclusion. It was observed that the Reciproc Blue instruments had higher cyclic fatigue resistance than VDW.ROTATE instruments (P<0.05). Recent studies have shown that reciprocal movement increases cyclic fatigue resistance compared to rotational movement. The VDW.ROTATE instrument, which has a similar size, design, and alloy as the Reciproc Blue instrument, can also be used by clinicians in reciprocating motion with endo motors capable of reciprocating in different directions. However, even if the cyclic fatigue resistance increases by using VDW.ROTATE instruments in reciprocation, the cyclic fatigue resistance is lower than Reciproc Blue instruments.

Comparison of the cyclic fatigue resistance of ProGlider, PathGlider and One G path-finding instruments.

Background . The aim of the present study was to compare the cyclic fatigue resistance of novel nickel titanium rotary pathfinding instruments. Methods . Twenty instruments were selected for each file system. A simulated stainless steel root canal, with a 90° angle of curvature and a curvature radius of 3 mm, was used for cyclic fatigue test of the ProGlider (#16, progressive taper: 0.02‒ 0.085), PathGlider (#15, taper: .03), and One G (#14, taper: .03) instruments. Statistical analyses were performed with oneway ANOVA (P=0.05). Post hoc Tukey tests were used to determine any statistically significant differences between the groups. Results . The ProGlider instruments exhibited significantly more cyclic fatigue resistance than both PathGlider and One G instruments (P<0.001). One G instruments had significantly more resistance to fracture than PathGlider instruments (P<0.05). Conclusion . ProGlider instruments had better cyclic fatigue resistance than PathGlider and One G instruments.

Comparison of anthropometric measurements for prediction of the atherosclerosis and liver histology in young adults with nonalcoholic fatty liver disease.

AIM: Anthropometry is a good evaluation tool that establishes the association between body fat distribution and metabolic risk factors precisely. The aim of this study was to test the association of anthropometric measurements with subclinical atherosclerosis and liver fibrosis. METHODS: A total of 78 patients with nonalcoholic fatty liver disease (NAFLD) patients who had no known cardiovascular disease risk factors and 26 volunteered healthy controls were enrolled. Patients with suspected fatty liver underwent a liver biopsy. BMI, waist circumference (WC), hip circumference, and neck circumference (NC) were measured. To detect the presence of subclinical atherosclerosis, carotid intima-media thickness and carotid-femoral pulse wave velocity (cf-PWV) were examined. RESULTS: NAFLD patients with fibrosis had higher NC, WC, and hip circumference levels, but no difference was observed between NAFLD patients without fibrosis and controls in these parameters. BMI was statistically different among the three groups (P < 0.05). After adjusting for confounding risk factors, the only significant parameter associated with histologic severity of NAFLD was WC, with odds ratio of 1.10. All anthropometric measurements were correlated positively with fibrosis, cf-PWV, and each other. While the association between BMI and cf-PWV remained significant, WC was found to be an independent risk factor for carotid intima-media thickness after adjustment of known cardiovascular risk factors. CONCLUSION: WC is the strongest predictor of liver fibrosis as the anthropometric indexes in patients with NAFLD. NC can be used as an additional useful screening test for the primary evaluation of patients with NAFLD, even if it is not an independent risk factor.

Inflammatory markers C-reactive protein and PLR in relation to HCC characteristics.

INTRODUCTION: Several markers of systemic inflammation, including blood C-reactive protein, platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) have been identified as independent prognosticators for hepatocellular carcinoma (HCC). METHODS: To attempt to understand the significance of these markers, they were examined in relation to 4 tumour parameters, namely maximum tumour diameter (MTD), tumour multifocality, portal vein thrombosis (PVT) and blood alpha-fetoprotein (AFP) levels. RESULTS: Using linear and logistic regression models, we found that C-reactive protein and PLR on single variables, were statistically significantly related to the tumour parameters. In a logistic regression final model, CRP was significantly related to MTD, AFP and PVT, and the Glasgow Index significantly related to MTD and AFP. Results of the area under the receiver operating characteristic curves (ROC), showed that the areas for PLR and CRP were statistically significant for high versus low MTD and for presence versus absence of PVT. CRP alone was significant for high versus low AFP. CONCLUSIONS: These analyses suggest that the prognostic usefulness of the inflammatory markers PLR and CRP (but not NLR) may be due to their reflection of parameter values for tumour growth and invasiveness.

C-Reactive Protein and Platelet-Lymphocyte Ratio as Potential Tumor Markers in Low-Alpha-Fetoprotein Hepatocellular Carcinoma.

The hepatocellular carcinoma (HCC) tumor marker alpha-fetoprotein (AFP) is only elevated in about half of the HCC patients, limiting its usefulness in following the effects of therapy or screening. New markers are needed. It has been previously noted that the inflammation markers C-reactive protein (CRP) and platelet-lymphocyte ratio (PLR) are prognostically important and may reflect HCC aggressiveness. We therefore examined these 2 markers in a low-AFP HCC cohort and found that for HCCs > 2 cm, both markers significantly rise with an increasing maximum tumor diameter (MTD). We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Youden index value for each marker, and their area-under-the-curve values for each MTD group. Patients were dichotomized into 2 groups based on the CRP and PLR from the receiver-operating characteristic curve analysis. In the logistic regression models of the 4 different MTD patient groups, CRP and PLR levels were statistically significant to estimate MTD in univariate logistic regression models of MTD groups > 2 cm. CRP and PLR were then combined, and the combination was statistically significant to estimate MTD groups of 3-, 4-, and 5-cm cutoffs. CRP and PLR thus have potential as tumor markers for low-AFP HCC patients, and possibly for screening.

Macroscopic Portal Vein Thrombosis in HCC Patients.

Macroscopic portal vein invasion (PVT) by hepatocellular carcinoma (HCC) in the liver is one of the most important negative prognostic factors for HCC patients. The characteristics of a large cohort of such patients were examined. We found that the percent of patients with PVT significantly increased with increasing maximum tumor diameter (MTD), from 13.7% with tumors of MTD <5cm to 56.4% with tumors of MTD >10cm. There were similar numbers of HCC patients with very large tumors with and without PVT. Thus, MTD alone was insufficient to explain the presence of PVT, as were high AFP levels, since less than 50% of high AFP patients had PVT. However, the percent of patients with PVT was also found to significantly increase with increasing blood alpha-fetoprotein (AFP) levels and tumor multifocality. A logistic regression model that included these 3 factors together showed an odds ratio of 17.9 for the combination of MTD>5.0cm plus tumor multifocality plus elevated AFP, compared to low levels of these 3 parameters. The presence or absence of macroscopic PVT may therefore represent different HCC aggressiveness phenotypes, as judged by a significant increase in tumor multifocality and AFP levels in the PVT positive patients. Factors in addition to MTD and AFP must also contribute to PVT development.

C-reactive protein and hepatocellular carcinoma: analysis of its relationships to tumor factors.

C-reactive protein (CRP) is a blood marker for inflammation and is an independent prognostic factor for many human cancers. Combined with albumin levels, it forms the basis of the Glasgow Index for cancer prognosis. We reviewed the literature on CRP and HCC and also evaluated blood CRP levels and combination CRP plus albumin levels in a large HCC cohort. In order to understand the prognostic significance of CRP, we retrospectively examined a large HCC cohort and examined the relationship of CRP levels to tumor parameters. We report, that CRP alone and CRP plus albumin combined as well, significantly correlated with parameters of HCC aggressiveness, such as maximum tumor dimension (MTD), portal vein thrombosis (PVT) and blood alpha-fetoprotein (AFP) levels, both as individual parameters and all parameters together (Aggressiveness Index). This extends current thinking, to suggest a possible explanation for the usefulness of blood CRP levels in HCC prognostication.

HCC with low- and normal-serum alpha-fetoprotein levels.

A large database of 1773 HCC patients in Turkey was examined. 41.9% had alpha-fetoprotein (AFP) levels <20 IU/ml and an additional 16.123% had values between 20-100 IU/ml. This 58% of the cohort (<100 IU/ml AFP levels) was examined in detail. 66% of patients with small (<5 cm) HCCs had low AFP, compared to 49% of patients with larger (>5 cm) HCCs. The mean diameter (MTD) of larger MTD, low AFP tumors was 8.4cm. Therefore, factors other than AFP must contribute to HCC tumor growth. Larger tumors in low AFP patients had both higher platelet levels and increased PVT percent. Linear regression analysis for both MTD and multifocality showed that platelet numbers and presence of PVT were significant variables; whereas for PVT, significant variables were albumin, alkaline phosphatase and MTD. Comparisons between patients with AFP levels <20, 20-<100, 100-<1000 and >1000 IU/ml showed the most significant tumor finding was an increase in PVT percent between each group, and to a lesser extent, MTD. Thus, low- or normal-AFP HCCs constitute the majority of patients and have slightly lower MTD and much lower PVT percent than HCCs associated with elevated blood AFP levels. New, non-AFP markers are thus needed, especially for small HCCs.

The association of fatty pancreas with subclinical atherosclerosis in nonalcoholic fatty liver disease.

INTRODUCTION: Ectopic fat accumulation in many tissues has been shown to be a risk factor for developing cardiovascular disease. No study to date has investigated whether fatty pancreas plays a role in the development of subclinical atherosclerosis. We aimed to assess the relationship between fatty pancreas and subclinical atherosclerosis in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) and healthy controls. PATIENTS AND METHODS: One hundred patients with biopsy-proven NAFLD and 38 healthy controls were included. Transabdominal ultrasonography examination was performed on all the cases with high-resolution ultrasonography (Acuson S3000) using 6 mHz convex probes. The measurements of carotid intima-media thickness (CIMT) and carotid-femoral pulse wave velocity (cf-PWV) were performed to investigate the relationship between fatty pancreas and atherosclerosis. RESULTS: The rate of newly diagnosed DM and prediabetes in the NAFLD patients was 6 and 21%, respectively. Most of the patients with NAFLD (97%) were found to have an increased echogenicity of the pancreas at ultrasound examination. Grade of fatty pancreas was correlated positively with cf-PWV levels (P<0.05), whereas no correlation was found with CIMT (P>0.05). The presence of fatty pancreas was associated significantly with higher CIMT and cf-PWV levels (P<0.05). The results for cf-PWV and CIMT did not remain significant after adjustment for confounding factors. Although the levels of cf-PWV and CIMT increased with increasing grade of fatty pancreas, there was no significant association. CONCLUSION: We have shown for the first time that fatty pancreas is a contributing factor for the development of atherosclerosis in patients with NAFLD. This study also confirms the strong association between NAFLD and fatty pancreas.

Characteristics of Hepatocellular Carcinoma Aggressiveness Factors in Turkish Patients.

A large cohort of hepatocellular carcinoma (HCC) patients from several collaborating Turkish institutions were examined for the tumor parameters of maximum diameter (MTD), portal vein thrombosis (PVT), and α-fetoprotein (AFP) levels. A relationship was found between MTD and blood platelet levels. Patients with large ≥5 cm tumors who had normal platelet levels had significantly larger tumors, higher percent of PVT, and significantly lower blood total bilirubin and liver cirrhosis than similar ≥5 cm tumor patients having thrombocytopenia. A comparison of patients with and without PVT showed significantly larger tumors, greater multifocality, blood AFP, and C-reactive protein levels, and, interestingly, lower HDL levels in the patients with PVT. Fifty-eight percent of the total cohort had AFP levels ≤100 IU/mL (and 42.1% had values ≤20 IU/mL). These patients had significantly smaller tumors, less tumor multifocality and percent PVT, lower total bilirubin, and less cirrhosis. There was considerable geographic heterogeneity within Turkey in the patterns of HCC presentation, with areas of higher and lower hepatitis B virus, hepatitis D virus, cirrhosis, and tumor aggressiveness parameters. Turkish patients thus have distinct patterns of presentation, but the biological relationships between MTD and both platelets and bilirubin levels are similar to the relationships that have been reported in other ethnic patient groups.

Effect of ProTaper Gold, Self-Adjusting File, and XP-endo Shaper Instruments on Dentinal Microcrack Formation: A Micro-computed Tomographic Study.

INTRODUCTION: The aim of the present study was to evaluate the frequency of dentinal microcracks observed after root canal preparation with ProTaper Universal (PTU; Dentsply Tulsa Dental Specialties, Tulsa, OK), ProTaper Gold (PTG; Dentsply Tulsa Dental Specialties), Self-Adjusting File (SAF; ReDent Nova, Ra'anana, Israel), and XP-endo Shaper (XP; FKG Dentaire, La Chaux-de-Fonds, Switzerland) instruments using micro-computed tomographic (CT) analysis. METHODS: Forty extracted human mandibular premolars having single-canal and straight root were randomly assigned to 4 experimental groups (n = 10) according to the different nickel-titanium systems used for root canal preparation: PTU, PTG, SAF, and XP. In the SAF and XP groups, the canals were first prepared with a K-file until #25 at the working length, and then the SAF or XP files were used. The specimens were scanned using high-resolution micro-computed tomographic imaging before and after root canal preparation. Afterward, preoperative and postoperative cross-sectional images of the teeth were screened to identify the presence of dentinal defects. For each group, the number of microcracks was determined as a percentage rate. The McNemar test was used to determine significant differences before and after instrumentation. The level of significance was set at P ≤ .05. RESULTS: The PTU system significantly increased the percentage rate of microcracks compared with preoperative specimens (P < .05). No new dentinal microcracks were observed in the PTG, SAF, or XP groups. CONCLUSIONS: Root canal preparations with the PTG, SAF, and XP systems did not induce the formation of new dentinal microcracks on straight root canals of mandibular premolars.

Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis.

BACKGROUND: Fecal microbial transplantation (FMT) provides to replace beneficial bacteria with more favorable microbiomes in recipient with dysbiosis. The aim of the present study was to prospectively investigate the efficacy of FMT by assessing the clinical and endoscopic response in patients with ulcerative colitis (UC) who had failed anti-inflammatory and immunosuppressive therapy. METHODS: In this prospective and uncontrolled study, 30 patients with UC were included. All medications except mesalazine were stopped 4 weeks before FMT. Colonoscopy was performed both before and after FMT. To assess the efficacy of FMT, Mayo scores were calculated at week 0 and week 12. A total of 500 mL extracted fresh fecal suspension was administered into the 30 to 40 cm proximal of terminal ileum of recipients. RESULTS: After FMT, 21 of the (70%) 30 patients showed clinical response, and 13 of the 30 (43.3%) patients achieved clinical and endoscopic remission at the week 12. Nine patients (30%) were accepted as a nonresponder at the end of the week 12. There was no significant difference among donors concerning both the rate of clinical remission and clinical response. No adverse events were observed in the majority of patients during FMT and 12 weeks follow-up. Seven patients (23.3%) experienced mild adverse events such as nausea, vomiting, abdominal pain, diarrhea, and fewer after FMT. CONCLUSION: FMT could be considered as a promising rescue treatment modality before surgery in patients with refractory UC. Besides, FMT also appears to be definitely safer and more tolerable than the immunosuppressive therapy in patients with UC (NCT02575040).