Genetic diversity of CYP3A5 and ABCB1 variants in East-Central and South European populations.

BACKGROUND: CYP3A5 enzyme encoded by CYP3A5 is important for drug metabolism in gut and liver, whereas P-glycoprotein by ABCB1, is an ATP-dependent drug efflux pump which exports endo- and exogenous substances outside the cell. AIM: The study was to assess the prevalence of CYP3A5 alleles: *1, *2, *3, *4, *6 and *7, and C and T of ABCB1 in Poles, Belarusians and Bosnians and to compare it with the data reported from other European populations. SUBJECTS AND METHODS: Overall, 511 unrelated healthy subjects from Poland (n = 239), Belarus (n = 104) and Bosnia and Herzegovina (n = 168) were included in this study. Allele frequencies and statistical parameters (AMOVA version 2.9.3) were determined. RESULTS: In Poles, Belarusians and Bosnians the *3 allele of CYP3A5 was the most common, and wild-type allele *1, were: 5.8%, 1.6% and 2.1%, respectively. Allele *2 was very rare, and alleles *4, *6 and *7 were not detected. For the populations mentioned above, the ABCB1 allele C was: 48.1%, 51.4%, 52.4%, respectively. CONCLUSION: In compared populations, the distribution of CYP3A5 variants but not ABCB1, differed significantly. Alleles *4, *6 and *7 of CYP3A5 did not occur or occurred rarely.

Magnitude dependent discordance in liver stiffness measurements using elastography point quantification with transient elastography as the reference test.

OBJECTIVES: To investigate diagnostic performance of point shear wave elastography by elastography point quantification (ElastPQ) for non-invasive assessment of liver fibrosis in patients with chronic liver diseases (CLD). METHODS: Liver stiffness measurement (LSM) by transient elastography (TE) and ElastPQ was performed in patients with CLD and healthy volunteers. The stage of liver fibrosis was defined by TE which served as the reference. We compared two methods by using correlation, area under the receiver operating characteristics curve (AUC) analysis, Bland and Altman plot and Passing-Bablok regression. RESULTS: A total of 185 subjects (20 healthy volunteers and 165 patients with CLD (128 non-alcoholic fatty liver disease), 83 (44.9%) females, median age 53 years, BMI 27.3 kg/m2) were evaluated. There were 24.3%, 13.5% and 11.4% patients in ≥ F2, ≥ F3 and F4 stage, respectively. The best performing cutoff LSM values by ElastPQ were 5.5 kPa for F ≥ 2 (AUC = 0.96), 8.1 kPa for F ≥ 3 (AUC = 0.98) and 9.9 kPa for F4 (AUC = 0.98). Mean (SD) difference between TE and ElastPQ measurements was 0.98 (3.27) kPa (95% CI 0.51-1.45, range 4.99-21.60 kPa). Two methods correlated significantly (r = 0.86; p < 0.001), yet Bland and Altman plot demonstrated difference between measurements, especially with TE values > 10 kPa. Passing and Bablok regression analysis yielded significant constant and proportional difference between ElastPQ and TE. CONCLUSION: ElastPQ is reliable method for assessment of liver fibrosis but LSM values are not interchangeable with TE, especially above 10 kPa. Diagnostic performance of ElastPQ for sub-classification of patients with compensated advanced chronic liver disease should therefore be furtherly investigated. KEY POINTS: • ElastPQ appears to be reliable method for assessment of liver fibrosis, with data presented here mostly applicable to NAFLD. • LSM values produced by TE and ElastPQ are NOT interchangeable-in values < 10 kPa, they are similar, but in values > 10 kPa, they appear to be increasingly and significantly different. • Diagnostic performance of ElastPQ for sub-classification of patients with compensated advanced chronic liver disease should be furtherly investigated.

Liver elastography malignancy prediction score for noninvasive characterization of focal liver lesions.

BACKGROUND & AIMS: To analyse elastographic characteristics of focal liver lesions (FLL)s and diagnostic performance of real-time two-dimensional shear-wave elastography (RT-2D-SWE) in order to differentiate benign and malignant FLLs. METHODS: Consecutive patients diagnosed with FLL by abdominal ultrasound (US) underwent RT-2D-SWE of FLL and non-infiltrated liver by intercostal approach over the right liver lobe. The nature of FLL was determined by diagnostic work-up, including at least one contrast-enhanced imaging modality (MDCT/MRI), check-up of target organs when metastatic disease was suspected and FLL biopsy in inconclusive cases. RESULTS: We analysed 196 patients (median age 60 [range 50-68], 50.5% males) with 259 FLLs (57 hepatocellular carcinomas, 17 cholangiocarcinomas, 94 metastases, 71 haemangiomas, 20 focal nodular hyperplasia) of which 70 (27%) were in cirrhotic liver. Malignant lesions were stiffer (P < .001) with higher variability in intralesional stiffness (P = .001). The best performing cut-off of lesion stiffness was 22.3 kPa (sensitivity 83%; specificity 86%; positive predictive value [PPV] 91.5%; negative predictive value [NPV] 73%) for malignancy. Lesion stiffness <14 kPa had NPV of 96%, while values >32.5 kPa had PPV of 96% for malignancy. Lesion stiffness, lesion/liver stiffness ratio and lesion stiffness variability significantly predicted malignancy in stepwise logistic regression (P < .05), and were used to construct a new Liver Elastography Malignancy Prediction (LEMP) score with accuracy of 96.1% in validation cohort (online calculator available at http://bit.do/lemps). CONCLUSION: The comprehensive approach demonstrated in this study enables correct differentiation of benign and malignant FLL in 96% of patients by using RT-2D-SWE.

Diclofenac sodium versus ceftazidime for preventing pancreatitis after endoscopic retrograde cholangiopancreatography: a prospective, randomized, controlled trial.

BACKGROUND AND AIMS: We aimed to compare the efficacy of prophylactic, parenterally administered ceftazidime and rectally applied diclofenac sodium for the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). METHODS: We prospectively enrolled patients who underwent ERCP. In a double-blind, randomized, controlled trial, patients received a suppository containing diclofenac sodium rectally (100 mg) and placebo intravenously (group A) or ceftazidime intravenously (1 g) and placebo rectally (group B) immediately before the procedure. The serum and urine amylase levels were recorded and the patients were clinically evaluated after ERCP. RESULTS: Of the 272 patients enrolled (group A: 129; group B: 143), 32 developed pancreatitis (group A: 11 [8.5 %]; group B: 21 [14.7 %]; P = 0.17; relative risk = 1.72; 95 % confidence interval [CI] = 0.86-3.43). The severity of the pancreatitis or complications did not significantly differ between the groups. A serum amylase level of ≥560 U/L and urine amylase level of ≥1150 U/L indicated a positive likelihood ratio for post-ERCP pancreatitis of ≥10. Moreover, the threshold visual analog scale score of ≤5 for abdominal pain after ERCP had excellent diagnostic potential for predicting the presence or absence of post-ERCP pancreatitis. CONCLUSIONS: The PEP incidence did not differ between the ceftazidime and diclofenac sodium groups. In patients with nonsteroidal anti-inflammatory drug contraindications, antibiotics can be considered a safe alternative to diclofenac sodium for PEP prevention. Moreover, the visual analog scale for abdominal pain has excellent diagnostic value for predicting PEP. CLINICAL TRIALS. GOV NUMBER: NCT 01784445.

Prevalence of genetic prothrombotic risk factors: 1691G > A FV, 20210G > A PT and 677C > T MTHFR mutations in the Bosnian population.

BACKGROUND: Venous thrombosis (VT) affects 1-2 out of 10(3) individuals each year. Mutations of 1691G > A FV gene, 20210G > A PT gene and 677C > T gene MTHFR are common in Europe and increase the risk of venous thrombosis. To the authors' knowledge, this is the first report on the prevalence of these mutations in the general population of Bosnia and Herzegovina. AIM: The aim of this study was to simultaneously analyse main VT associated polymorphisms and compare the results with those published for other European populations. DATA SOURCES: Electronic databases including Medline and Embase were searched from 1995 to December 2013. SUBJECTS AND METHODS: The subjects of the study consisted of 100 unrelated healthy people from Bosnia and Herzegovina (82 female and 18 male). The mean age of the cohort was 58.8 (± 10.7) years. PCR-RFLP was used for measurement of allele frequencies. RESULTS: All three SNPs were found to be polymorphic, with allele frequencies of 6.0%, 6.0% and 37.5% for 1691A FV, 20210A PT and 677T MTHFR, respectively. CONCLUSION: Further studies on larger cohorts with an adequate female-to-male ratio are necessary to confirm a high prevalence of hereditary thrombophilia in the Bosnian population.

FibroTest/Fibrosure for significant liver fibrosis and cirrhosis in chronic hepatitis B: a meta-analysis.

OBJECTIVES: Extent of liver fibrosis is one of the most important factors in determining prognosis and the need for active treatment in chronic hepatitis B (CHB). Noninvasive alternatives such as FibroTest/Fibrosure (FT) have been developed in order to overcome the shortcomings of liver biopsy (LB). We aimed to systematically review studies describing the diagnostic accuracy of FT for predicting CHB-related fibrosis. METHODS: MEDLINE and EMBASE searches and hand searching methods were performed to identify studies that assessed the diagnostic accuracy of FibroTest in HB patients using LB as a reference standard. We used a hierarchical summary receiver operating curves model and the bivariate model to produce summary receiver operating characteristic curves and pooled estimates of sensitivity and specificity. RESULTS: We included 16 studies (N=2494) and 13 studies (N=1754) in the heterogenous meta-analysis for liver fibrosis and cirrhosis, respectively. The area under the hierarchical summary receiver operating curve for significant liver fibrosis and for all included studies was 0.84 (95% confidence interval (CI): 0.78-0.88). At the FT threshold of 0.48, the sensitivity, specificity, and diagnostic odds ratio (DOR) of FT for significant fibrosis were 61 (48-72%), 80 (72-86%), and 6.2% (3.3-11.9), respectively. The area under the hierarchical summary receiver operating curve for liver cirrhosis and for all included studies was 0.87 (95% CI: 0.85-0.90). At the FT threshold of 0.74, the sensitivity, specificity, and DOR of FT for cirrhosis were 62 (47-75%), 91 (88-93%), and 15.7% (8.6-28.8), respectively. CONCLUSIONS: FibroTest is of value in exclusion of patients with CHB-related cirrhosis, but has suboptimal accuracy in the detection of significant fibrosis and cirrhosis. It is necessary to further improve the test or combine it with other noninvasive modalities in order to improve accuracy.

Artificial neural network predicts the need for therapeutic ERCP in patients with suspected choledocholithiasis.

BACKGROUND: Selection of patients with the highest probability for therapeutic ERCP remains an important task in a clinical workup of patients with suspected choledocholithiasis (CDL). OBJECTIVE: To determine whether an artificial neural network (ANN) model can improve the accuracy of selecting patients with a high probability of undergoing therapeutic ERCP among those with strong clinical suspicion of CDL and to compare it with our previously reported prediction model. DESIGN: Prospective, observational study. SETTING: Single, tertiary-care endoscopy center. PATIENTS: Between January 2010 and September 2012, we prospectively recruited 291 consecutive patients who underwent ERCP after being referred to our center with firm suspicion for CDL. INTERVENTIONS: Predictive scores for CDL based on a multivariate logistic regression model and ANN model. MAIN OUTCOME MEASUREMENTS: The presence of common bile duct stones confirmed by ERCP. RESULTS: There were 80.4% of patients with positive findings on ERCP. The area under the receiver-operating characteristic curve for our previously established multivariate logistic regression model was 0.787 (95% CI, 0.720-0.854; P < .001), whereas area under the curve for the ANN model was 0.884 (95% CI, 0.831-0.938; P < .001). The ANN model correctly classified 92.3% of patients with positive findings on ERCP and 69.6% patients with negative findings on ERCP. LIMITATIONS: Only those variables believed to be related to the outcome of interest were included. The majority of patients in our sample had positive findings on ERCP. CONCLUSIONS: An ANN model has better discriminant ability and accuracy than a multivariate logistic regression model in selecting patients for therapeutic ERCP.

Machine Learning for Short-Term Mortality in Acute Decompensation of Liver Cirrhosis: Better than MELD Score.

Prediction of short-term mortality in patients with acute decompensation of liver cirrhosis could be improved. We aimed to develop and validate two machine learning (ML) models for predicting 28-day and 90-day mortality in patients hospitalized with acute decompensated liver cirrhosis. We trained two artificial neural network (ANN)-based ML models using a training sample of 165 out of 290 (56.9%) patients, and then tested their predictive performance against Model of End-stage Liver Disease-Sodium (MELD-Na) and MELD 3.0 scores using a different validation sample of 125 out of 290 (43.1%) patients. The area under the ROC curve (AUC) for predicting 28-day mortality for the ML model was 0.811 (95%CI: 0.714- 0.907; p < 0.001), while the AUC for the MELD-Na score was 0.577 (95%CI: 0.435-0.720; p = 0.226) and for MELD 3.0 was 0.600 (95%CI: 0.462-0.739; p = 0.117). The area under the ROC curve (AUC) for predicting 90-day mortality for the ML model was 0.839 (95%CI: 0.776- 0.884; p < 0.001), while the AUC for the MELD-Na score was 0.682 (95%CI: 0.575-0.790; p = 0.002) and for MELD 3.0 was 0.703 (95%CI: 0.590-0.816; p < 0.001). Our study demonstrates that ML-based models for predicting short-term mortality in patients with acute decompensation of liver cirrhosis perform significantly better than MELD-Na and MELD 3.0 scores in a validation cohort.

Application of Deep Learning for Real-Time Ablation Zone Measurement in Ultrasound Imaging.

BACKGROUND: The accurate delineation of ablation zones (AZs) is crucial for assessing radiofrequency ablation (RFA) therapy's efficacy. Manual measurement, the current standard, is subject to variability and potential inaccuracies. AIM: This study aims to assess the effectiveness of Artificial Intelligence (AI) in automating AZ measurements in ultrasound images and compare its accuracy with manual measurements in ultrasound images. METHODS: An in vitro study was conducted using chicken breast and liver samples subjected to bipolar RFA. Ultrasound images were captured every 15 s, with the AI model Mask2Former trained for AZ segmentation. The measurements were compared across all methods, focusing on short-axis (SA) metrics. RESULTS: We performed 308 RFA procedures, generating 7275 ultrasound images across liver and chicken breast tissues. Manual and AI measurement comparisons for ablation zone diameters revealed no significant differences, with correlation coefficients exceeding 0.96 in both tissues (p < 0.001). Bland-Altman plots and a Deming regression analysis demonstrated a very close alignment between AI predictions and manual measurements, with the average difference between the two methods being -0.259 and -0.243 mm, for bovine liver and chicken breast tissue, respectively. CONCLUSION: The study validates the Mask2Former model as a promising tool for automating AZ measurement in RFA research, offering a significant step towards reducing manual measurement variability.

Short-term efficacy of vedolizumab in patients with inflammatory bowel disease in real-life settings in Bosnia and Herzegovina.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), necessitates effective management strategies. This study aims to evaluate the real-world efficacy of vedolizumab, a newer biological therapy, in treating IBD in Bosnia and Herzegovina. A retrospective observational study was conducted across 6 medical centers, involving 139 IBD patients, 76 with UC and 63 with CD. Patients were assessed for clinical remission and other outcomes at the 26-week mark post vedolizumab treatment initiation. At 26 weeks, clinical remission was achieved in 82.9% of UC patients and 85.7% of CD patients. Mucosal healing was observed in 38.1% of CD patients. The efficacy of vedolizumab did not significantly differ based on prior anti-tumor necrosis factor (TNF) exposure. Notably, the clinical scoring tools for predicting vedolizumab response showed limited applicability in this cohort. Vedolizumab demonstrated high efficacy in treating both UC and CD in a real-world settings in Bosnia and Herzegovina, underscoring its potential as a significant therapeutic option in IBD management.

Predictive score for anastomotic leakage after elective colorectal cancer surgery: a decision making tool for choice of protective measures.

BACKGROUND: Anastomotic leakage is the most severe complication after colorectal surgery and a major cause of postoperative morbidity and mortality. We aimed to identify a predictive score for postoperative leakage after colorectal cancer surgery and to evaluate its usefulness in assessing various protective measures. METHODS: A total of 159 patients were divided into test (79 patients) and validation (40 patients) groups in order to identify the risk factors and construct the predictive score. The remaining 40 patients (intervention group) were prospectively evaluated with the application of protective measures guided by risk stratification according to the predictive score. RESULTS: A total of 23 of 159 (14.5 %) patients had anastomotic leakage, with 7 of 23 (30.4 %) of them needing reoperation. 11 of 159 (6.9 %) patients died, with 10 (6.3 %) deaths directly associated with anastomotic leakage. The rate of leakage in the test and validation groups (nonintervention group) was 22 of 119 (18.5 %), while the rate of leakage in the intervention group was 3 of 40 (7.5 %). The odds ratio for anastomotic leakage in the intervention group was 0.23 compared to the nonintervention group, with a relative risk reduction of 73 % for unfavorable event. The number needed to treat was 8 patients. There were also 10 of 119 (8.4 %) deaths in the nonintervention group compared to 1 of 40 (2.5 %) in the intervention group (Fisher's test; p = 0.18). CONCLUSIONS: Our simple predictive score may be a valuable decision making tool that can help surgeons reliably identify patients at high risk for postoperative anastomotic leakage and apply guided intraoperative protective measures.

Celiac disease in adult population in Tuzla region of Bosnia and Herzegovina: a 3-year surveillance (2007-2009).

BACKGROUND: there is no epidemiological estimation of the incidence and prevalence of CDin the adult population in Bosnia and Herzegovina(B&H), nor there are reports about the clinical presentation of CDin patients in B&H. AIM: to assess the epidemiological and clinical characteristics of CDin the adult population in Tuzla Canton in northeast of Bosnia and Herzegovina. METHODS: we retrospectively analyzed all hospital records of both adult inpatients and outpatients evaluated in University Clinical Center Tuzla, with suspected CD and residing in Tuzla Canton of B&H between 1.1.2007 and 31.12.2009. RESULTS: during the 3-year period we registered 42 cases of celiac disease (CD) with 31/42 (73.8%) of female and 11/42 (26.2%) of male patients - male to female ratio 1 to 2.82. The average annual crude incidence of CD during the observed period was 2.55/105 population (%95 CI=1.74-3.36). The average crude incidence in men was 1.51/105 and 4.08/105 in women. The average annual standardized incidence during the time period 2007-2009 was 1.89/105 (%95 CI=1.32-2.56). The sum prevalence during the study period was 7.66/105 population. Prevalence among men was 4.53/105 and 12.23/105 among women. CONCLUSIONS: The incidence of CD in our region is demonstrating a steep rise and apparently low prevalence in our region is merely a result of poor availability of diagnostics in previous years.

Helicobacter pylori resistance to clarithromycin and quinolones in patients with dyspepsia in Tuzla Canton, Bosnia and Herzegovina.

Aim To evaluate Helicobacter pylori (H. pylori) resistance to clarithromycin and quinolones in patients with dyspepsia in Tuzla Canton, Bosnia and Herzegovina, a region with no data on clarithromycin or quinolones resistance. Methods A prospective cross-sectional study was conducted at the Department of Gastroenterology and Hepatology at University Clinical Centre Tuzla between January 2021 and June 2022. The study included 99 patients who underwent esophagogastroduodenoscopy (EGDS) due to dyspepsia. In all patients biopsies were taken for rapid urease test (RUT) and histology findings, concomitantly with blood samples for IgG serology. All RUT positive patient samples were tested for clarithromycin and quinolones susceptibility with GenoType HelicoDr, a PCR method which detects point mutations in 23S rRNA and mutations in the gyrA gene. Results Out of 99 dyspeptic patients, 67 (67.7%) were serologically positive to H. pylori, 46 (46.4.%) were RUT positive, and 19 (19.2 %) had a positive histology finding. Antibiotic (AB) resistance was tested in the total of 46/99 (46.4%) patients. Resistance to clarithromycin was detected in 28.26% (13/46), quinolones resistance in 36.96% (17/46) , and resistance to both AB was detected in 8.69% (4/46) tested biopsies. Conclusions Due to high clarithromycin and quinolones resistance rates, we recommend the use of bismuth quadruple or non-bismuth concomitant quadruple therapy for H. pylori eradication in Tuzla Canton, Bosnia and Herzegovina.

[The influence of corticosteroid therapy on development of osteoporosis in Crohn's disease]. / Uticaj kortikosteroidne terapije na nastanak osteoporoze u Kronovoj bolesti.

Systemic corticosteroids (CS) are often used in treatment of Crohn's disease and are usually considered the main cause of osteoporosis in patients with Crohn's disease. The aim of this paper was to assess the influence of CS on development of osteoporosis in Crohn's disease. In this study bone mass density (BMD) was analyzed in 43 patients with Crohn's disease. Most of the examined patients (72.1%) used CS for more than 3 months. Osteoporosis was diagnosed in 30.2% of patients, and osteopenia in 44.2% of patients. There were no statistically significant difference in BMD among patients who were on CS and the ones who were not. In the group of newly diagnosed patients 60% had reduced bone density, opposing 61.6% of patients with previously diagnosed disease. There was no statistically significant difference among those two groups of patients. Risk factor such as corticosteroid therapy is not independent risk factor for reduced BMD. Newly diagnosed patients have high prevalence of reduced BMD and they were not on CS therapy, which suggest that possible inflammatory nature of the disease is a possible risk factor for reduced BMD in Crohn's disease.

Inflammatory bowel disease in Tuzla Canton, Bosnia-Herzegovina: A prospective 10-year follow-up.

BACKGROUND: The incidence and prevalence of inflammatory bowel disease (IBD) vary between regions but have risen globally in recent decades. A lack of data from developing nations limits the understanding of IBD epidemiology. AIM: To perform a follow-up review of IBD epidemiology in the Tuzla Canton of Bosnia-Herzegovina during a 10-year period (2009-2019). METHODS: We prospectively evaluated the hospital records of both IBD inpatients and outpatients residing in Tuzla Canton for the specified period of time between January 1, 2009 and December 31, 2019. Since all our patients had undergone proximal and distal endoscopic evaluations at the hospital endoscopy unit, we used the hospital's database as a primary data source, alongside an additional cross-relational search of the database. Both adult and pediatric patients were included in the study. Patients were grouped by IBD type, phenotype, age, and gender. Incidence rates were calculated with age standardization using the European standard population. Trends in incidence and prevalence were evaluated as a 3-year moving average and average annual percentage change rates. RESULTS: During the 10-year follow-up period, 651 patients diagnosed with IBD were monitored (of whom 334, or 51.3%, were males, and 317, or 48.7%, were females). Of all the patients, 346 (53.1%) had been diagnosed with ulcerative colitis (UC), 292 (44.9%) with Crohn's disease (CD), and 13 (2%) with indeterminate colitis (IC). We observed 440 newly diagnosed patients with IBD: 240 (54.5%) with UC, 190 (43.2%) with CD, and 10 (2.3%) with IC. The mean annual crude incidence rates were found to be 9.01/100000 population for IBD [95% confidence interval (CI): 8.17-9.85], with 4.91/100000 (95%CI: 4.29-5.54) for UC and 3.89/100000 (95%CI: 3.34-4.44) for CD. Calculated IBD prevalence in 2019 was 146.64/100000 (95%CI: 128.09-165.19), with 77.94/100000 (95%CI: 68.08-87.70) for UC and 65.77/100000 (95%CI: 54.45-74.1) for CD. The average annual IBD percentage change was 0.79% (95%CI: 0.60-0.88), with -2.82% (95%CI: -2.67 to -2.97) for UC and 6.92% (95%CI: 6.64-7.20) for CD. During the study period, 24,509 distal endoscopic procedures were performed. The incidence of IBD was 3.16/100 examinations (95%CI: 2.86-3.45) or 1.72/100 examinations (95%CI: 1.5-1.94) for UC and 1.36/100 examinations (95%CI: 1.17-1.56) for CD. CONCLUSION: Trends in the incidence and prevalence of IBD in Tuzla Canton are similar to Eastern European averages, although there are significant epidemiological differences within geographically close and demographically similar areas.

Liver and Nonliver-Related Outcomes at 2 Years Are Not Influenced by the Results of the FIB-4 Test and Liver Elastography in a Real-Life Cohort of Patients with Type 2 Diabetes.

Aims: To investigate morbidity and mortality in a real-life cohort of patients with type 2 diabetes (T2D) in relation to prevalence and severity of nonalcoholic fatty liver disease (NAFLD). Methods: Patients with T2D were referred for assessment of liver fibrosis by the FIB-4 test and liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE). Liver steatosis was quantified by the controlled attenuation parameter (CAP). These patients were followed until death or censored date. Results: Among 454 patients (52% males, mean age 62.5 years, BMI 30.9 kg/m2), 82.6% was overweight, 77.8% had fatty liver, and 9.9% and 3.1% had LSM and FIB-4 values suggestive of advanced fibrosis, respectively. During the follow-up period of median 2 years, 106 (23%) patients experienced adverse event (11% cardiovascular) and 17 (3.7%) died, whereas no liver-related morbidity or mortality was observed. Independent predictors of adverse outcomes were age and higher platelet count, while FIB-4, LSM, and CAP were not. Conclusion: In a cohort of T2D patients, no liver-related morbidity or mortality occurred during 2 years. Our patients probably have low real prevalence of advanced fibrosis which is likely overestimated by LSM ≥ 9.6 kPa. Liver fibrosis may be safely reassessed in the 2 years interval in noncirrhotic patients with T2D.

Concordance of non-invasive serology-based scoring indices and transient elastography for liver fibrosis and cirrhosis in chronic hepatitis C.

Aim To assess concordance of eight frequently used serology-based scoring indices for liver fibrosis and cirrhosis with transient elastography (TE) in chronic hepatitis C (CHC) patients in order to determine serum indices with the highest concordance and clinical usability in clinical practice. Methods In this prospective study, 63 CHC patients were included and TE results were compared with eight non-invasive indices. The diagnostic performance of these tests was assessed using receiver operating characteristic curves with kappa index calculated for the concordance analysis. Results Median age of 63 patients was 54 years (interquartile range: 42 to 63); 27 (42.9%) were females. According to areas under the Receiver Operating Characteristics (AUROC), the best performing serum markers for significant liver fibrosis (METAVIR ≥F2), advanced liver fibrosis (≥F3) and cirrhosis (F4) determined by TE measurements (≥7.1kPa, ≥9.5kPa and ≥12kPa, respectively) were Fibrotest (AUROC=0.727 for ≥F2) and FIB-4 score (AUROC=0.779 for ≥F3 and AUROC=0.889 for F4). Fibrotest cut-off at >0.50 was concordant with TE for presence of significant fibrosis in 30 (out of 45; 66.7%), FIB-4 cut-off at <1.45 was concordant for absence of significant fibrosis in 13 (out of 18; 72.2%) and Goeteborg University Cirrhosis Index (GUCI) cut-off at >1 was concordant for presence of cirrhosis in 16 (out of 22; 72.7%) patients, but not for exclusion of cirrhosis. Conclusion Serology-based scoring indices had moderate overall concordance with TE. We propose that FIB-4 score, Fibrotest and GUCI be used in routine practice to exclude and diagnose significant fibrosis and diagnose cirrhosis, respectively.

Diagnostic Performance of 2-D Shear-Wave Elastography with Propagation Maps and Attenuation Imaging in Patients with Non-Alcoholic Fatty Liver Disease.

We aimed to investigate the diagnostic performance of new 2-D shear-wave elastography (SWE) with propagation maps and attenuation imaging (ATI) for quantification of fibrosis and steatosis in non-alcoholic fatty liver disease (NAFLD). Consecutive patients with NAFLD and healthy volunteers underwent liver stiffness measurement and steatosis quantification by means of vibration-controlled transient elastography coupled with the controlled attenuation parameter as the reference and by 2-D shear-wave elastography (2-D-SWE) with propagation maps and ATI as the investigational methods. We included 232 participants (164 in the NAFLD group and 68 in the healthy control group): 51.7%/49.3% women/men; mean age, 54.2 ± 15.2 y; mean body mass index, 29.4 ± 6.5 kg/m2. Significant correlations were found between 2-D-SWE and vibration-controlled transient elastography (r = 0.71, p < 0.0001) and between ATI and the controlled attenuation parameter (r = 0.72, p < 0.0001). NAFLD-specific 2-D-SWE liver stiffness measurement cutoffs were as follows-F ≥ 2: 7.9 kPa (area under the curve [AUC] = 0.91); F ≥ 3: 10 kPa (AUC = 0.92); and F = 4: 11.4 kPa (AUC = 0.95). For steatosis, the best cutoffs by ATI were as follows-S1 = 0.73 dB/cm/MHz (AUC = 0.86); S2 = 0.76 dB/cm/MHz (AUC = 0.86); and S3 = 0.80 dB/cm/MHz (AUC = 0.83). According to Baveno VI criteria, the optimal 2-D-SWE liver stiffness measurement for diagnosing liver cirrhosis is 15.5 kPa (AUC = 0.94), and for ruling out compensated advanced chronic liver disease it is 9.2 kPa (AUC = 0.92). To conclude, 2-D-SWE with propagation maps and ATI is reliable for quantification of liver fibrosis and steatosis in patients with NAFLD.