Search

Population screening; Liver fibrosis; Early diagnosis Cribratge de població; Fibrosi hepàtica; Diagnòstic precoç Cribado de población; Fibrosis hepática; Diagnóstico precoz Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate −18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression. LiverScreen Consortium and the European Commission under the H20/20 program (847989); AGAUR (2017SGR-01281); Centro de Investigacion Biomedica en Enfermedades Hepaticas y Digestivas; Fundación de Investigación Sanitaria, cofunded by Instituto Carlos III–Subdirección General de Evaluación and the European Regional Development Fund (PI18/01330, PI18/00662, and PI18/00862); and Gilead’s Investigator–sponsored research program (IN-ES-989-5309)

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/m(2). 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.

We evaluated the diagnostic accuracy of the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) measured with either an M or XL probe against liver biopsy (LB) in patients with non-alcoholic fatty liver disease (NAFLD). This study was a cross-sectional prospective study that included 179 NAFLD patients. With a cutoff value for CAP >= 345, we can exclude significant steatosis in 87% (79.4%-92.5%) of our population. With respect to the LSM, the highest accuracy was obtained for F >= F3 (area under the receiver operating characteristic curve [AUROC] = 0.98) and F = F4 (AUROC = 0.98). In a multivariable linear regression model, significant predictors influencing LSM were fibrosis stage (beta = 2.6, p < 0.001) as a positive predictor and lobular inflammation (beta = -0.68, p = 0.04) as a negative predictor, without significant influence after adjustment for CAP and probe type. We found that CAP is a satisfactory method for excluding advanced steatosis, while LSM is a good non-invasive marker for the exclusion of fibrosis.

Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation. A wide range of adipokines activities suggests they influence pathogenesis and infection course. The aim was to assess concentrations of chemerin, omentin, and vaspin among COVID-19 patients with an emphasis on adipokines relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. Serum chemerin, omentin and vaspin concentrations were measured in serum collected from 70 COVID-19 patients at the moment of admission to hospital, before any treatment was applied and 20 healthy controls. Serum chemerin and omentin concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers (271.0 vs. 373.0 ng/ml; p p = 0.01, respectively). There were no correlations of analyzed adipokines with COVID-19 severity based on the presence of pneumonia, dyspnea, or necessity of Intensive Care Unit hospitalization (ICU). Liver test abnormalities did not influence adipokines levels. Elevated GGT activity was associated with ICU admission, presence of pneumonia and elevated concentrations of CRP, ferritin and interleukin 6. Chemerin and omentin depletion in COVID-19 patients suggests that this adipokines deficiency play influential role in disease pathogenesis. However, there was no relationship between lower adipokines level and frequency of COVID-19 symptoms as well as disease severity. The only predictive factor which could predispose to a more severe COVID-19 course, including the presence of pneumonia and ICU hospitalization, was GGT activity.

Simple Summary Non-alcoholic fatty liver disease (NAFLD) is expected to become the leading cause of hepatocellular carcinoma (HCC) in the near future. In this article, we review the current knowledge about the epidemiology, risk factors, pathogenesis, clinical presentation and diagnostic approach to HCC in NAFLD. Knowledge of these facts is of great importance to improve the early identification of patients that are at risk, allowing for early detection of HCC and, thus, an improvement in clinical outcomes. This is especially important given that around 30% of NAFLD-related HCCs develop in a non-cirrhotic liver. The presence of diabetes, male sex, older age and Hispanic race, in addition to liver cirrhosis, are the most important risk factors for HCC in this setting. In summarising the current knowledge of genetic susceptibility, metabolic derangements and immunological mechanisms involved in the pathogenesis of NAFLD-related HCC, we illustrate the need for further research on this intriguing topic. Abstract Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of liver morbidity worldwide and, as such, represents the pathogenic background for the increasing incidence of hepatocellular carcinoma (HCC). The annual incidence of NAFLD-related HCC is expected to increase by 45–130% by 2030. Diabetes mellitus is the most important risk factor for HCC development in NAFLD, with the risk further increased when associated with other metabolic traits, such as obesity, arterial hypertension and dyslipidemia. The highest risk of HCC exists in patients with advanced fibrosis or cirrhosis, although 20–50% of HCC cases arise in NAFLD patients with an absence of cirrhosis. This calls for further investigation of the pathogenic mechanisms that are involved in hepatocarcinogenesis, including genetics, metabolomics, the influence of the gut microbiota and immunological responses. Early identification of patients with or at risk of NAFLD is of utmost importance to improve outcomes. As NAFLD is highly prevalent in the community, the identification of cases should rely upon simple demographic and clinical characteristics. Once identified, these patients should then be evaluated for the presence of advanced fibrosis or cirrhosis and subsequently enter HCC surveillance programs if appropriate. A significant problem is the early recognition of non-cirrhotic NAFLD patients who will develop HCC, where new biomarkers and scores are potential solutions to tackle this issue.

Background: Liver involvement in Coronavirus disease 2019 (COVID-19) has been recognised. We aimed to investigate the correlation of non-invasive surrogates of liver steatosis, fibrosis and inflammation using transient elastography (TE) and FibroScan-AST (FAST) score with (a) clinical severity and (b) 30-day composite outcome of mechanical ventilation (MV) or death among patients hospitalized due to COVID-19. Method: Patients with non-critical COVID-19 at admission were included. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed by TE. Clinical severity of COVID-19 was assessed by 4C Mortality Score (4CMS) and need for high-flow nasal cannula (HFNC) oxygen supplementation. Results: 217 patients were included (66.5% males, median age 65 years, 4.6% with history of chronic liver disease). Twenty-four (11.1%) patients met the 30-day composite outcome. Median LSM, CAP and FAST score were 5.2 kPa, 274 dB/m and 0.31, respectively, and neither was associated with clinical severity of COVID-19 at admission. In multivariate analysis FAST &gt, 0.36 (OR 3.19, p = 0.036), 4CMS (OR 1.68, p = 0.002) and HFNC (OR 7.03, p = 0.001) were independent predictors of adverse composite outcome. Conclusion: Whereas LSM and CAP failed to show correlation with COVID-19 severity and outcomes, FAST score was an independent risk factor for 30-day mortality or need for MV.

Background: Derangement of liver blood tests (LBT) is frequent in patients with Coronavirus disease 2019 (COVID-19). We aimed to evaluate (a) the prevalence of deranged LBT as well as their association with (b) clinical severity at admission and (c) 30-day outcomes among the hospitalized patients with COVID-19. Methods: Consecutive patients with COVID-19 hospitalized in the regional referral center over the 12-month period were included. Clinical severity of COVID-19 at hospital admission and 30-day outcomes (need for intensive care, mechanical ventilation, or death) were analyzed. Results: Derangement of LBT occurred in 2854/3812 (74.9%) of patients, most frequently due to elevation of AST (61.6%), GGT (46.1%) and ALT (33.4%). Elevated AST, ALT, GGT and low albumin were associated with more severe disease at admission. However, in multivariate Cox regression analysis, when adjusted for age, sex, obesity and presence of chronic liver disease, only AST remained associated with the risk of dying (HR 1.5081 and 2.1315, for elevations 1–3 × ULN and &gt, 3 × ULN, respectively) independently of comorbidity burden and COVID-19 severity at admission. Patients with more severe liver injury more frequently experienced defined adverse outcomes. Conclusions: Deranged LBTs are common among patients hospitalized with COVID-19 and might be used as predictors of adverse clinical outcomes.

Analysis of liver biopsy specimens showed that SARS-CoV-2 might have led to liver damage. This study aimed to evaluate the role of selected hepatokines and myokines in the development and progression of COVID-19. Seventy patients with laboratory-confirmed COVID-19 and 20 healthy volunteers were enrolled in the study. Irisin, pentraxin 3, fetuin-A, and FGF-21 serum concentrations and biochemical parameters were assessed using an immunoenzymatic method with commercially available enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) kits. Serum fetuin-A concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers. The serum concentration of FGF-21 was significantly increased in obese COVID-19 patients compared to overweight ones. Moreover, the FGF-21 level was higher in COVID-19 patients diagnosed with metabolic syndrome than in patients without metabolic syndrome. PTX3 concentration was higher in COVID-19 patients with higher HOMA-IR values than those with lower HOMA-IR values. COVID-19 patients with HOMA-IR ≤ 3 and &gt, 3 had significantly lower fetuin-A levels than the control group. Irisin concentration was significantly decreased in the HOMA-IR ≤ 3 COVID-19 subgroup when comparing with the control group. Lower levels of fetuin-A observed in COVID-19 patients despite higher HOMA-IR, CRP, and ferritin levels, pneumonia, patients requiring ICU care suggests that fetuin-A deficiency predisposes to more severe COVID-19 course. Upregulated pentraxin 3 may be used as a potential predictor of COVID-19 severity.

Nonalcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disease worldwide, associated with epidemics of overweight and resulting metabolic syndrome (MetS). Around 20–30% of patients with NAFLD develop progressive liver fibrosis, which is the most important predictor of liver-related and overall morbidity and mortality. In contrast to classical understanding, no significant association has been demonstrated between the inflammatory component of NAFLD, i.e., nonalcoholic steatohepatitis (NASH), and the adverse clinical outcomes. Older age (>50 years) and presence of type 2 diabetes mellitus, in addition to some genetic variants, are most consistently reported indicators of increased risk of having liver fibrosis. However, critical driving force for the progression of fibrosis and risk factors for this have still not been fully elucidated. Apart from the genetic profile, gut dysbiosis, weight gain, worsening of insulin resistance, and worsening of liver steatosis represent candidate factors associated with unfavourable development of liver disease. Cardiovascular events, extrahepatic malignancies, and liver-related deaths are the leading causes of mortality in NAFLD. As patients with advanced fibrosis are under highest risk of adverse clinical outcomes, efforts should be made to recognize individuals under risk and rule out the presence of this stage of fibrosis, preferably by using simple noninvasive tools. This process should start at the primary care level by using validated biochemical tests, followed by direct serum tests for fibrosis or elastography in the remaining patients. Patients with advanced fibrosis should be referred to hepatologists for aggressive lifestyle modification and correction of the components of MetS, and cirrhotic patients should be screened for hepatocellular carcinoma and oesophageal varices.

Background and aims: The impact of hemodialysis on liver stiffness is still unclear. The aim of the study was to assess liver fibrosis by real-time two-dimensional shear wave elastography (RT 2D- SWE) and to quantify the influence of net fluid withdrawal on liver stiffness during one hemodialysis session. The second aim was to investigate the influence of systolic blood pressure and time spent on dialysis (in years) on liver stiffness measurements. Methods: This before/after hemodialysis (HD) study in a group of end stage renal disease (ESRD) patients was carried out with patients on regular HD. Measurements of liver stiffness were done using RT 2D-SWE directly before and after a hemodialysis session. Results: In this study 27 patients with mean age 69.4 ± 14.75 years were included. Mean net fluid withdrawal volume per session was 2874.07 ± 778.35 ml. Mean pre-HD and post-HD liver stiffness measurements were 8.15 kPa (95% confidence interval, CI 7.61-8.68) and 6.70 kPa (95% CI 6.10- 7.30 kPa), respectively. Mean liver stiffness reduction was 1.448 ± 1.14 kPa. The amount of fluid removed correlated with the decline in liver stiffness values after HD (ρ = 0.523, P = 0.003). There was a positive but statistically not significant correlation between time spent in HD and liver stiffness (ρ = 0.151, P = 0.623) CONCLUSION: Liver stiffness significantly declined after one session of HD. The change in liver stiffness was strongly correlated with the amount of net fluid withdrawal. Random liver stiffness measurements (LSM) by RT 2D-SWE does not precisely show the degree of fibrosis, Furthermore, it is presumed that postdialysis liver stiffness values likely reflect the real degree of liver fibrosis.

Aim: To assess the potential of the soluble transforming growth factor β receptor type III (sTGFβrIII), a key regulator in TGFβ signaling, as a biomarker for diagnosis and stratification of patients with acute pancreatitis (AP). ------ Methods: In this small prospective pilot study, patients' (N=22) plasma samples were obtained at three time points: the first and fourth day of hospitalization and the day of hospital discharge. Healthy controls' plasma (N=25) was obtained at a single time point. Concentration of sTGFβrIII in plasma was determined by ELISA. Data were analyzed by fitting linear or linear mixed models. ----- Results: Plasma sTGFβrIII levels at presentation (day 1) were similar in AP patients and healthy participants, irrespectively of the disease severity. sTGFβrIII levels in patients were constant during hospital stay. ----- Conclusion: These observations do not support further evaluation of plasma sTGFβrIII levels in this setting, but do not exclude a potential biological role of TGFβ and membrane-bound TGFβrIII in AP pathophysiology.

Background and aims: We aimed to validate newly proposed noninvasive criteria for diagnosing clinically significant portal hypertension (CSPH) using liver stiffness measurements (LSM) by transient elastography (TE) and platelet count. ----- Methods: Diagnostic performance of these new criteria for CSPH (LSM ≥ 25 kPa to rule in and Plt ≥ 150 × 109/L + LSM ≤ 15 kPa to rule out CSPH) were retrospectively tested in an independent cohort of consecutive patients who underwent hepatic venous pressure gradient (HVPG) measurements and liver biopsy due to suspicion of compensated advanced chronic liver disease. Suspicion of cACLD was based on LSM ≥ 10 kPa by TE or results of liver imaging, without overt signs of CSPH. Patients with conditions known to affect results of LSM (ALT > 5 × ULN, liver congestion, extrahepatic biliary obstruction, infiltrative liver neoplasms) were excluded. ----- Results: Seventy six (76) patients were included: 78.9% males, mean age 62 years, 36.8% suffered from alcoholic, 30.3% nonalcoholic fatty liver disease, 14.5% chronic viral hepatitis, 30.3% were obese, 52.6% had HVPG ≥ 10 mmHg, 56.6% had platelet count ≥ 150 × 109/L. LSM ≥ 25 kPa had 88.9% specificity (95% CI 73.9-96.9) to rule in, whereas Plt ≥ 150 + LSM ≤ 15 kPa had 100% sensitivity (95% CI 91.1-100) to rule out CSPH. ----- Conclusion: By using these simple noninvasive criteria 49/76 (64.5%) patients could be classified correctly for the presence/absence of CSPH, thus obviating the need for HVPG measurements.

Objective: To identify pretreatment laboratory parameters associated with treatment response and to describe the relationship between treatment response and liver decompensation in patients with primary biliary cholangitis treated with ursodeoxycholic acid. Methods: We defined treatment response as both ALP ≤ 1.67 × ULN and total bilirubin ≤ 2 × ULN. Multiple logistic regression analyses were performed to adjust for confounding effects of sociodemographic variables. Results: Pretreatment total bilirubin ((TB), OR = 0.3388, 95%CI = 0.1671–0.6077), ALT (OR = 0.5306, 95%CI = 0.3830–0.7080), AST (OR = 0.4065, 95%CI = 0.2690–0.5834), ALP (OR = 0.3440, 95%CI = 0.2356–0.4723), total cholesterol ((TC), OR = 0.7730, 95%CI = 0.6242–0.9271), APRI (OR = 0.3375, 95%CI = 0.1833–0.5774), as well as pretreatment albumin (OR = 1.1612, 95%CI = 1.0706–1.2688) and ALT/ALP (OR = 2.4596, 95%CI = 1.2095–5.5472) were associated with treatment response after six months of treatment. Pretreatment TB (OR = 0.2777, 95%CI = 0.1288–0.5228), ALT (OR = 0.5968, 95%CI = 0.4354–0.7963), AST (OR = 0.4161, 95%CI = 0.2736–0.6076), ALP (OR = 0.4676, 95%CI = 0.3487–0.6048), APRI (OR = 0.2838, 95%CI = 0.1433–0.5141), as well as pretreatment albumin (OR = 1.2359, 95%CI = 1.1257–1.3714) and platelet count (OR = 1.0056, 95%CI = 1.0011–1.0103) were associated with treatment response after 12 months of treatment. Treatment response after 6 months of UDCA therapy is significantly associated with treatment response after 12 months of UDCA therapy (OR = 25.2976, 95% CI = 10.5881–68.4917). Treatment responses after 6 and 12 months of UDCA therapy decrease the risk of an episode of liver decompensation in PBC patients (OR = 12.1156, 95%CI = 3.7192–54.4826 and OR = 21.6000, 95%CI = 6.6319–97.3840, respectively). Conclusions: There are several pretreatment laboratory parameters associated with treatment response in patients with primary biliary cholangitis. Treatment response after six months is significantly associated with treatment response after 12 months of ursodeoxycholic acid (UDCA) therapy. Treatment responses after 6 and 12 months of UDCA decrease the risk of an episode of liver decompensation.

Background: Ursodeoxycholic acid response score (URS) is a prognostic model that estimates the baseline probability of treatment response after 12 months of ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cholangitis (PBC). ------ Aim: To independently evaluate the predictive performance of the URS model. ----- Methods: We used a cohort of Slovak and Croatian treatment-naïve PBC patients to quantify the discrimination ability using the area under receiver operating characteristic curve (AUROC) and its 95% confidence interval (CI). Furthermore, we evaluated the calibration using calibration belts. The primary outcome was treatment response after 12 months of UDCA therapy defined as values of alkaline phosphatase ≤1.67 × upper limit of normal. ----- Results: One hundred and ninety-four patients were included. Median pretreatment age was 56 years (interquartile range 49-62). Treatment response was achieved in 79.38% of patients. AUROC of the URS was 0.81 (95% CI 0.73-0.88) and the calibration belt revealed that response rates were correctly estimated by predicted probabilities. ----- Conclusion: Our results confirm that the URS can be used in treatment-naïve PBC patients for estimating the treatment response probability after 12 months of UDCA therapy.

According to the recent data presented by Central-European HCV experts, the estimated prevalence of HCV is between 0.2% and 1.7% in certain countries in this region. There are no financial limitations to access to treatment in most countries. Patients in these countries have access to at least one pangenotypic regimen. The most common barriers to the elimination of HCV in Central Europe are a lack of established national screening programmes and limited political commitment to the elimination of HCV. Covid-19 has significantly affected the number of patients who have been diagnosed and treated, thus, delaying the potential elimination of HCV. These data suggest that the elimination of HCV elimination projected by WHO before 2030 will not be possible in the Central Europe.

ObjectiveLiver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients.DesignThis international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation.ResultsAfter screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM.ConclusionThe M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.

What is known and Objective: There is no optimal standardized model in the transfer of care between hospitals and primary healthcare facilities. Transfer of care is a criti- cal point during which unintentional discrepancies, that can jeopardize pharmacother- apy outcomes, can occur. The objective was to determine the effect that an integrated medication reconciliation model has on the reduction of the number of post-discharge unintentional discrepancies. Methods: A randomized controlled study was conducted on an elderly patient popu- lation. The intervention group of patients received a medication reconciliation model, led entirely by a hospital clinical pharmacist (medication reconciliation at admission, review and optimization of pharmacotherapy during hospitalization, patient education and counselling, medication reconciliation at discharge, medication reconciliation as part of primary health care in collaboration with a primary care physician and a community pharmacist). Unintentional discrepancies were identified by comparing the medications listed on the discharge summary with the first list of medications prescribed and issued at primary care level, immediately after discharge. The main outcome measures were incidence, type and potential severity of post-discharge un- intentional discrepancies. Results and discussion: A total of 353 patients were analysed (182 in the intervention and 171 in the control group). The medication reconciliation model, led by a hospital clinical pharmacist, significantly reduced the number of patients with unintentional discrepancies by 57.1% (p < 0.001). The intervention reduced the number of patients with unintentional discrepancies associated with a potential moderate harm by 58.6% (p < 0.001) and those associated with a potential severe harm by 68.6% (p = 0.039). The most common discrepancies were incorrect dosage, drug omission and drug commission. Cardiovascular medications were most commonly involved in unintentional discrepancies. What is new and Conclusion: The integrated medication reconciliation model, led by a hospital clinical pharmacist in collaboration with all health professionals involved in the patient's pharmacotherapy and treatment, significantly reduced unintentional discrepancies in the transfer of care.

Aim: To explore the prognostic value of modified Discriminant Function (mDF), Glasgow Alcoholic Hepatitis Score (GAHS), Model of End Stage Liver Disease (MELD), Age-Bilirubin-International Normalized Ratio-Creatinine score (ABIC), and the Lille Model for the 28- and 90-day mortality in patients with alcoholic hepatitis. ----- Methods: This retrospective study enrolled patients treated for alcoholic hepatitis in Dubrava University Hospital between January 2014 and May 2018. The diagnosis was established based on histology findings or the combination of patient´s history of ongoing alcohol consumption before hospitalization, serum bilirubin above 50 mmol/L, and aspartate transaminase to alanine transaminase ratio greater than 1.5. We calculated mDF, MELD, GAHS, and ABIC on the first and seventh day of hospitalization (including the Lille model). ----- Results: In total, 70 patients were enrolled. ABIC at admission most accurately predicted the 28-day mortality, with a cut-off of 9.92 (AUC 0.727; 95% CI 0.608-0.827, P=0.0119), while GAHS most accurately predicted the 90-day mortality, calculated both at admission (cut off >7, AUC 0.765, 95% CI 0.639-0.864, P8, AUC 0.835 95% CI 0.716-0.918, P

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.

Background The potentially inappropriate medications (PIMs) and drug–drug interactions (DDIs) can significantly affect patient safety in the elderly, especially at transition of health care. Objective The aim of this study is to evaluate PIMs involved in potentially clinically significant DDIs in prescribed pharmacotherapy of elderly patients at hospital discharge. Setting Internal Medicine Clinic of University Hospital Dubrava, Zagreb, Croatia. Method During a 16- month period, the pharmacotherapy data were assessed using Lexicomp Online screening software to identify category C (monitor drug therapy), D (consider therapy modification) and X (avoid combination) DDIs. The European Union (EU)(7)-PIM criteria were applied to detect inappropriately prescribed medications involved in DDIs. Clinical pharmacists obtained data from patients’ medical records and patient/caregiver interviews. Main outcome measure The incidence of PIMs involved in potentially clinically significant DDIs. Results A total of 364 consecutive elderly patients were enrolled in the study. The mean number of prescription medications at discharge was 9.3. Overall, 2833 potentially clinically significant DDIs were identified: 2445 (86.3%) of them were category C, 347 (12.3%) category D and 41 (1.4%) were category X interactions. A total of 1164 PIMs were involved in 31.2% of category C interactions, 60.2% of category D interactions and 43.9% of category X interactions. The most frequent PIMs involved in potentially clinically significant DDIs were tramadol, benzodiazepines, moxonidine, vildagliptin and metoclopramide. Conclusion A very high incidence of DDIs in elderly patients and a high incidence of PIMs involved in DDIs was determined at hospital discharge.

Background: Infections are common in patients with liver cirrhosis and increase mortality. We explored the relationship between infection and liver dysfunction in their effects on mortality. ----- Methods: Single-center data on decompensated liver cirrhosis patients hospitalized between March 2014 and December 2017 (index period) were reviewed until death, liver transplantation or 31 December 2018. Infections were classified as community-acquired infection (CAi) or hospital/healthcare associated infection (HCAi). Child-Pugh, model for the end-stage liver disease (MELD) and chronic liver failure-organ failure (CLiF-OF) scores indicated liver (dys)function. ----- Results: We enrolled 155 patients (85% alcoholic liver disease), 65 without infection at first hospitalization, 48 with CAi and 42 with HCAi. Multidrug resistant agents were confirmed in 2/48 (4.2%) CAi and 10/42 (23.8%) HCAi patients. At first hospitalization, infection was independently associated with worse liver dysfunction and vice versa, and with higher 30-day mortality [odds ratio (OR) = 2.73, 95% confidence interval (CI) 1.07-6.94]. The association was reduced with adjustment for MELD/CLiF-OF scores, but mediation analysis detected an indirect (via liver dysfunction) association. Twenty-eight patients were repeatedly hospitalized, 11 with new HCAi. HCAi was independently associated with twice higher risk of medium-term mortality and added an additional risk to any level of liver dysfunction, considering all or patients who survived the first 30 days. In those repeatedly hospitalized, HCAi appeared independently associated with a higher probability of infection and higher MELD scores at subsequent hospitalizations. ----- Conclusion: Infection (particularly HCAi) adds mortality risk to any level of liver dysfunction in decompensated liver cirrhosis patients. Mechanisms of long(er)-term effects (in acute episode survivors) seemingly include enhanced deterioration of liver function.

Ultrasound (US) is usually the first and most commonly used tool in the diagnostic algorithm for liver disease. It is widely available, non-invasive and offers a real-time assessment of the liver in several anatomic planes, using different US modalities such as greyscale imaging, Doppler, elastography and contrast-enhanced US. This multiparametric ultrasound (MPUS) provides more information of the examined structures and allows for a faster and more accurate diagnosis, usually at the point of care, thus reducing the requirement for some invasive and more expensive methods. Current data on the MPUS in hepatology are summarised in this review, mostly focused on its use for non-invasive staging of liver fibrosis, detection and classification of portal hypertension and oesophageal varices, prognosis in chronic liver diseases and characterisation of focal liver lesions (FLLs). Based on the available data, we propose practical algorithms for clinical use of MPUS in chronic liver disease and FLL.

We have read with great interest manuscript by Piccinni et al. in which they demonstrated significant prevalence of liver steatosis in patients with compensated advanced chronic liver disease (cACLD), previously assumed to decrease in advanced fibrosis, as well as very good performance of Controlled attenuation parameter (CAP) in this cohort of patients (1, 2).

Aims To examine the temporal changes of both controlled attenuation parameter (CAP) and liver stiffness measurements (LSM), assessed by Fibroscan, in a large sample of patients with non-alcoholic fatty liver disease (NAFLD). Methods In this prospective, observational study, we consecutively enrolled 507 adult individuals with Fibroscan-defined NAFLD who were followed for a mean period of 21.2 ± 11.7 months. Results During the follow-up period, 84 patients (16.5%) had a progression of CAP of at least 20% with a median time of 39.93 months, while 201 (39.6%) patients had a progression of LSM of at least 20% with median time of 30.46 months. There were significant differences in the proportion of LSM progression across body mass index (BMI) categories, with obese patients having the highest risk of progression over the follow-up (hazard ratio 1.66; 95%CI 1.23–2.25). Multivariable regression analysis showed that BMI and serum creatinine levels were the strongest predictors for CAP progression in the whole population, while HOMA-estimated insulin resistance was an independent predictor of LSM progression over time in the subgroup of obese patients. Conclusion This prospective study shows for the first time that the progression risk of both liver steatosis and fibrosis, detected non-invasively by Fibroscan, is relevant and shares essentially the same metabolic risk factors that are associated with NAFLD progression detected by other invasive methods.

Aim To evaluate the impact of pharmacotherapeutic education on 30-day post-discharge medication adherence and adverse outcomes in patients with type 2 diabetes mellitus (T2DM). Methods The prospective, randomized, single-center study was conducted at the Medical Department of University Hospital Dubrava, Zagreb, between April and June 2018. One hundred and thirty adult patients with T2DM who were discharged to the community were randomly assigned to either the intervention or the control group. Both groups during the hospital stay received the usual diabetes education. The intervention group received additional individual pre-discharge pharmacotherapeutic education about the discharge prescriptions. Medication adherence and occurrence of adverse outcomes (adverse drug reactions, readmission, emergency department visits, and death) were assessed at the follow-up visit, 30 days after discharge. Results The number of adherent patients was significantly higher in the intervention group (57/64 [89.9%] vs 41/61 [67.2%]; χ2 test, P = 0.003]. There was no significant difference between the groups in the number of patients who experienced adverse outcomes (31/64 [48.4%] vs 36/61 [59.0%]; χ2 test, P = 0.236). However, higher frequencies of all adverse outcomes were consistently observed in the control group. Conclusion Pharmacotherapeutic education of patients with T2DM can significantly improve 30-day post-discharge medication adherence, without a significant reduction in adverse clinical outcomes. ClinicalTrial.gov identification number: NCT03438162

AIM: To compare and evaluate the hepatoprotective effect of remote ischemic preconditioning (RIPC) with local ischemic preconditioning (LIPC) of the liver during human liver resections. ----- METHODS: A prospective, single-centre, randomised control trial was conducted in the Clinical Hospital "***" from April 2017 to January 2018. A total of 60 patients, who underwent liver resection due to colorectal cancer liver metastasis, were randomised to one of three study arms: 1) a RIPC group, 2) an LIPC group and 3) a control group (CG) in which no ischemic preconditioning was done before liver resection. The hepatoprotective effect was evaluated by comparing serum transaminase levels, bilirubin levels, albumin, and protein levels, coagulograms and through pathohistological analysis. The trial was registered on ClinicalTrials.gov (NCT****). ----- RESULTS: Significant differences were found in serum levels of liver transaminases and bilirubin levels between the groups, the highest level in the CG and the lowest level in the LIPC group. Levels of cholinesterase were also significantly higher in the LIPC group. Pathohistological findings graded by the Rodriguez score showed favourable changes in the LIPC and RIPC groups versus the CG. ----- CONCLUSION: Strong evidence supports the hepatoprotective effect of RIPC and LIPC preconditioning from an ischemia-reperfusion injury of the liver. Better synthetic liver function preservation in these two groups supports this conclusion.

The aim of the study was to explore predictive value of the ALBI, PALBI and MELD scores on survival in patients resected for hepatocellular carcinoma with compensated liver cirrhosis and no macrovascular infi ltration. In this retrospective study, longitudinal survival analysis was performed. We analyzed patient/tumor characteristics and MELD, ALBI and PALBI scores as liver function tests for predicting survival outcome. Survival was analyzed from the date of liver resection until death, liver transplantation, or end of follow-up. Patients were stratifi ed for age, cirrhosis etiology, presence of esophageal varices, hepatocellular carcinoma stage, microvascular invasion, histologic diff erentiation, and resection margins. We identifi ed 38 patients (alcoholic cirrhosis in 84.2% of patients) resected over an 8-year period. Median preoperative MELD score was 8, ALBI score -2.63, and PALBI score -2.38. During the follow-up period, 24 patients died. Estimated median survival time was 36 months. Microvascular invasion was observed in 33 patients. Higher ALBI score was associated with 23.1% higher relative risk of death. PALBI score was associated with 12.1% higher relative risk of death, whereas MELD score was not associated with the risk of death. In conclusion, ALBI score demonstrated signifi cant predictive capabilities for survival in patients with compensated cirrhosis resected for hepatocellular carcinoma., Cilj je bio istražiti prediktivnu vrijednost zbira ALBI, PALBI i MELD za preživljenje bolesnika s kompenziranom cirozom reseciranih zbog hepatocelularnog karcinoma bez makrovaskularne invazije. Provedena je retrospektivna longitudinalna analiza preživljenja. Testirane su karakteristike bolesnika/tumora kao i jetreni funkcijski testovi MELD, ALBI i PALBI za predviđanje preživljenja. Bolesnici su praćeni nakon resekcije jetre do smrti, transplantacije jetre odnosno do kraja vremena praćenja. Bolesnici su kategorizirani po dobi, etiologiji ciroze, prisutnosti varikoziteta jednjaka, stadiju karcinoma, mikrovaskularnoj invaziji, histološkom stadiju i resekcijskim rubovima. Identifi cirali smo 38 bolesnika (alkoholna ciroza kod 84,2% bolenika) reseciranih kroz razdoblje od 8 godina. Medijan prijeoperacijskog zbira MELD bio je 8, zbira ALBI -2,63 i zbira PALBI -2,38. Tijekom praćenja 24 bolesnika su umrla. Očekivani medijan preživljenja iznosio je 36 mjeseci. Mikrovaskularna invazija pronađena je u 33 bolesnika. Veći ALBI je bio povezan s 23,1%, a PALBI s 12,1% većim relativnim rizikom od smrtnog ishoda. MELD nije bio povezan sa smrtnim ishodom. Zbir ALBI je pokazao značajnu prediktivnu vrijednost preživljenja u skupini bolesnika s kompenziranom cirozom reseciranih zbog hepatocelularnog karcinoma.

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 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.

Liver fibrosis is a progressive pathological process resulting in an accumulation of excess extracellular matrix proteins. We discovered that bone morphogenetic protein 1-3 (BMP1-3), an isoform of the metalloproteinase Bmp1 gene, circulates in the plasma of healthy volunteers and its neutralization decreases the progression of chronic kidney disease in 5/6 nephrectomized rats. Here, we investigated the potential role of BMP1-3 in a chronic liver disease. Rats with carbon tetrachloride (CCl4)-induced liver fibrosis were treated with monoclonal anti-BMP1-3 antibodies. Treatment with anti-BMP1-3 antibodies dose- dependently lowered the amount of collagen type I, downregulated the expression of Tgfb1, Itgb6, Col1a1, and Acta2 and upregulated the expression of Ctgf, Itgb1, and Dcn. Mehanistically, BMP1-3 inhibition decreased the plasma levels of transforming growth factor beta 1(TGFb1) by prevention of its activation and lowered the prodecorin production further suppressing the TGFb1 profibrotic effect. Our results suggest that BMP1-3 inhibitors have significant potential for decreasing the progression of fibrosis in liver cirrhosis.

Aim of the study To collect and analyse data obtained from HCV opinion leaders/experts from central European countries, on factors which can affect the WHO target of HCV elimination by 2030. Material and methods Data were collected from opinion leaders/experts involved in management of HCV infections in Central European countries which participated in 9th Conference of the Central European Hepatologic Collaboration (Warsaw, 10-11 October 2019). A dedicated questionnaire collected current information related to HCV elimination in Bulgaria, Croatia, the Czech Republic, Hungary, Latvia, Lithuania, Poland and Slovakia. Results The HCV prevalence rate in particular countries varied from 0.2% to 1.7%. In most central European countries all the HCV infected population is eligible for reimbursement of treatment. However, in some countries there are still some limitations related to the stage of the disease and people who inject drugs. All countries have access to at least one pangenotypic regimen. The most common barrier to HCV elimination in all countries is insufficient political will to establish priority for HCV. None of the reporting countries has established a national screening programme. Conclusions Access to therapy for HCV is similar and the majority of patients in Central Europe can be treated according to the current guidelines. Unfortunately there are still some limitations and a lack of political will to implement national screening programmes. According to collected data HCV elimination will not be possible in the region by 2030.

Dijagnoza bolesti nealkoholne masne jetre (engl. non-alcoholic fatty liver disease, NAFLD) počinje već na temelju kliničkih obilježja bolesnika. Tipičan rizični profil predstavlja bolesnik s prekomjernom tjelesnom težinom, pogotovo ako su tome pridruženi šećerna bolest tipa 2, arterijska hipertenzija i/ili hiperlipidemija, uz uvjet isključene rizične konzumacije alkohola. Postojanje masne jetre najčešće se utvrđuje ultrazvukom na kojem je jetra svjetlija (ehogenija) u odnosu na korteks bubrega. Ultrazvukom se ne može prepoznati blaže oblike steatoze kada je < 20 – 30 % hepatocita masno transformirano. Elastografskim metodama može se kvantificirati stupanj steatoze i stadij fibroze. Stadij fibroze je najznačajniji prognostički čimbenik, dok je značaj upalne aktivnosti dvojben, a stupanj steatoze ne utječe bitno na ishod bolesti jetre. Za neinvazivnu procjenu steatoze i fibroze koriste se i biokemijski testovi, od najjednostavnijih dobivenih iz rutinskih laboratorijskih nalaza do složenih koji uključuju cirkulirajuće makromolekule i komponente izvanstaničnoga matriksa. Neinvazivne metode su pouzdane za isključivanje ciroze, no imaju relativno skromnu pozitivnu prediktivnu vrijednost, jer često precjenjuju stadij fibroze i ne daju informaciju o aktivnosti upale. Objektivniju dijagnozu ovih histoloških komponenti i time pouzdanu prognostičku informaciju pruža biopsija jetre. Obradu bolesnika s NAFLD-om treba započeti na primarnoj razini zdravstvene zaštite jednostavnim biokemijskim testom (npr. FIB-4) kojim se isključuje značajna fibroza. U slučaju povišenih vrijednosti potreban je potvrdni test (najbolje elastografija). Ako taj nalaz isključi značajnu fibrozu, bolesnik ostaje u skrbi obiteljskoga liječnika, a u slučaju teške fibroze/ciroze bolesnik se nastavlja liječiti kod specijaliste. Na ovaj način za 80 % se smanjuje upućivanje bolesnika specijalisti, te za pet puta poboljšava otkrivanje značajne fibroze/ciroze., Diagnosing non-alcoholic fatty liver disease (NAFLD) begins with analysing patient’s clinical features. The typical risk profile includes an overweight patient with comorbidities such as type 2 diabetes mellitus, arterial hypertension and/or hyperlipidaemia, excluding harmful alcohol consumption. Ultrasonography is the most widely used diagnostic tool for detecting fatty liver, which has higher echogenicity, i.e. is lighter in colour, compared to renal cortex. However, ultrasound cannot detect mild steatosis where < 20 – 30% of hepatocytes have been infiltrated by fat. Elastographic methods are used for grading steatosis and staging fibrosis. Liver fibrosis stage is the most significant prognostic indicator. On the other hand, the relevance of inflammatory activity is questionable and the degree of steatosis has no significant impact on the outcome of the disease. Steatosis and fibrosis can be evaluated using non-invasive biochemical tests, ranging from simple routine laboratory tests to more complex tests that include circulating macromolecules and components of extracellular matrix. Non-invasive methods provide reliable results for the exclusion of cirrhosis; however, their positive predictive value is relatively modest, as they often over-estimate the fibrosis stage and provide no information on inflammatory activity. Liver biopsy provides a more objective diagnosis of the histological features and, as a result, a more reliable prognosis. The workup of NAFLD patients should start at the primary healthcare level, with simple biochemical tests such as FIB-4, which excludes significant fibrosis. Elevated results need to be additionally confirmed by another test, most preferably elastography. If this test excludes significant fibrosis, the patient remains under the care of a primary care physician, and if it detects severe fibrosis/cirrhosis, the patient is referred to specialist treatment. This pathway has resulted in an 80 % decrease in referrals to a specialist and a 5-fold improvement in the detection of significant fibrosis/cirrhosis.

COVID-19 je infektivna bolest koja se nakon pojave (prosinac 2019., Wuhan, Kina) tijekom sljedeća 3 mjeseca proširila na sve kontinente i izazvala pandemiju s kojom je čovječanstvo prvi put suočeno. S obzirom na to da bolesnici imaju pretežito respiratornu simptomatologiju često s razvojem intersticijske upale pluća te da se radi o visoko kontagioznoj bolesti, nameće se potreba brze, pouzdane i sigurne dijagnostike plućnih komplikacija ove bolesti. U COVID-19 bolesnika ciljani ultrazvuk pluća je superioran u odnosu na klasičnu Rtg snimku srca i pluća te se u dijagnostičkoj pouzdanosti približio MSCT-u toraksa. Razlog tomu je činjenica da su upalni infiltrati lokalizirani prvenstveno bazalno i periferno gdje su dostupni UZV pregledu. Najčešće zahvaćene regije su 5 i 6 obostrano, a u nalazu dominiraju multiple B linije u 2 i više regija u kombinaciji s pojedinačnim B linijama. U ožujku 2020. osnovan je Primarni respiracijsko-intenzivistički centar u KB Dubrava (PRIC KBD) s ciljem zbrinjavanja COVID-19 bolesnika s umjerenom do teškom kliničkom slikom i znacima respiracijske insuficijencije. Za dijagnostiku i praćenje bolesnika, uz Rtg snimku srca i pluća te MSCT toraksa, korišten je ciljani UZV pluća. Osim dobre korelacije s kliničkom slikom i stupnjem respiracijske insuficijencije, ciljani UZV pluća pokazao se korisnim zbog kratke izloženosti aerosolu tijekom pretrage, a bez potrebe za mobilizacijom bolesnika ili korištenjem mobilnog Rtg uređaja. Postao je suverena zamjena za stetoskop uz mogućnost pridržavanja svih mjera za prevenciju širenja aerosola: mobilni uređaj bez kabela, mogućnost dezinfekcije pa čak i korištenje samo jednog uređaja po bolesniku u intenzivističkom centru, čime je postao važna dijagnostička metoda kod COVID-19 pozitivnih bolesnika., COVID-19 is an infectious disease which surfaced in December 2019 (Wuhan, China) and swept across all the continents in a matter of 3 months, triggering a pandemic faced by humanity for the first time. Given the predominance of respiratory symptoms in patients, often accompanied by the development of interstitial pneumonia, and the fact that it is a highly contagious disease, it called for a prompt, reliable and safe diagnosis of pulmonary complications of the disease. In COVID-19 patients, focused lung ultrasound is superior to the classical heart or chest X-ray, and in terms of diagnostic reliability, is almost up to par to an MSCT of the thorax. This is due to the fact that inflammatory infiltrates are localized primarily basally and peripherally where they are accessible to ultrasound examinations. Regions 5 and 6 (both sides) are most commonly affected, and medical reports show a predominance of multiple B lines in 2 or more regions in combination with individual B lines. In March 2020, the Primary Respiratory Intensive Care Center at Clinical Hospital Dubrava (PRIC KBD) was founded to treat COVID-19 patients with a moderate to severe clinical picture and signs of respiratory failure. In addition to an X-ray of the heart and lungs and MSCT of the thorax, patients were diagnosed and monitored using focused lung ultrasound. Besides a good correlation with the clinical picture and degree of respiratory failure, focused lung ultrasound has shown to be favorable due to short aerosol exposure during screening, without the need to mobilize patients or use a mobile X-ray device. It has become an unrivalled replacement for the stethoscope, capable of adhering to all measures to prevent the spread of aerosols: a cordless mobile device, disinfectable, with even the ability to use only one device per patient in the intensive care unit, rendering it an important diagnostic tool in COVID-19 positive patients.

Results from the interferon era have demonstrated reversibility of cirrhosis following viral eradication, but only for patients in the initial stage of cirrhosis. Although direct-acting antivirals (DAA) represent revolutionary treatment of hepatitis C, there are currently no studies showing histological effects of therapy on a large number of cirrhotic patients. However, studies involving transient elastography demonstrated a rapid decrease in liver stiffness after successful DAA therapy, probably due to resolution of inflammation, rather than fibrosis regression, as the latter requires a longer period of time. Reversal of fibrosis and cirrhosis upon viral eradication is a prerequisite for the reduction of portal pressure, but this effect has only been observed for the subclinical stage of portal hypertension (PH). On the other hand, the majority of patients with clinically significant PH remain at risk of decompensation and death, despite hepatitis C virus cure, as PH remains high in this setting. This calls for novel therapeutic approaches.

Cilj istraživanja: Cilj je ovog rada prikazati klinička iskustva našeg centra s oboljelima od hereditarne hemoragijske teleangiektazije (HHT). Prikazali smo kliničku sliku svojih bolesnika, nove dijagnostičke i terapijske mogućnosti, kao i svjetske smjernice u dijagnostici bolesti. Ispitanici i metode: U ovu retrospektivnu studiju uključeno je 13-ero bolesnika liječenih u Klinici za unutarnje bolesti KB-a Dubrava u razdoblju od 2008. do 2017. godine. Rezultati: Bilo je 9 muškaraca i 4 žene u dobi između 45 i 80 godina (medijan 70 godina). Svih 13-ero bolesnika prezentiralo se sideropeničnom anemijom i rekurentnim epistaksama koje su ujedno bile i najraniji znak bolesti. Dvanaestero bolesnika imalo je mukokutane teleangiektazije, a njih devetero gastrointestinalna krvarenja. U jednog bolesnika dokazana je pulmonalna, a kod još jednoga hepatalna arteriovenska malformacija. Nakon medijana praćenja od 60 mjeseci devetero je bolesnika živo, a njih četvero preminulo je. Zaključci: Prava dijagnoza bolesti u većine naših bolesnika postavljena je tek u starijoj dobi iako su se simptomi javljali i puno prije. U Republici Hrvatskoj ne postoje točni podaci o broju oboljelih, kao ni smjernice za otkrivanje i liječenje komplikacija bolesti. Nužno je formiranje multidisciplinarnih timova radi unaprjeđenja dijagnostike, ranijeg otkrivanja komplikacija bolesti te sveobuhvatnijeg praćenja bolesnika., Aim: The aim of this study is to present our center’s clinical experience with hereditary haemorrhagic telangiectasia (HHT). Herein, we showed clinical presentations of our patients, new diagnostic and therapeutic options, as well as the international guidelines for HHT diagnosis. Patients and methods: In this retrospective study, we identified 13 patients that were treated at the Department of Medicine, Clinical Hospital Dubrava from 2008 to 2017. Results: There were nine men and four women aged between 45 and 80 years (median 70 years). All 13 patients presented with sideropenic anaemia and recurrent epistaxis that was the earliest sign of the disease. Twelve patients had mucocutaneous telangiectasia, and nine patients were presented with gastrointestinal bleeding. One patient was diagnosed with pulmonary arteriovenous malformation, and the other one with hepatic malformation. After a median follow-up of 60 months, nine patients are alive, and four patients died. Conclusion: Most of our patients were diagnosed in older age, although the symptoms appeared much earlier in life. There are no data on the number of patients with HHT in the Republic of Croatia. Also, guidelines for diagnosis and screening for complications are lacking. Therefore, it is necessary to form a multidisciplinary team for diagnostic improvement, early detection of complications, and more intensive monitoring of patients.

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.

Aim: To assess the measures of disease frequency and determine the clinical features of primary biliary cholangitis (PBC) in two Croatian regions. Methods Databases of two tertiary hospitals, one located in the continental and one in the coastal region of Croatia, were retrospectively searched for PBC patients diagnosed from 2007 to 2018. Epidemiologic data analysis was restricted to patients from each hospital’s catchment area. We analyzed factors related to response to therapy and event-free survival (EFS), defined as absence of ascites, variceal bleeding, encephalopathy, hepatocellular carcinoma, liver transplantation (LT), or death. In addition, we determined clinical and demographic data of transplanted PBC patients. ----- Results: Out of 83 PBC patients, 86.7% were female, with a median age at diagnosis of 55 years. Average PBC incidence for the 11-year period was 0.79 and 0.89 per 100 000 population, whereas the point prevalence on December 31, 2017 was 11.5 and 12.5 in the continental and coastal region, respectively. Of 76 patients with complete medical records, 21% had an advanced disease stage, 31.6% had an associated autoimmune condition, and all received ursodeoxycholic acid. EFS rate at 5 years was 95.8%. In an age and sex-adjusted multivariate Cox regression model, the only factor significantly associated with inferior EFS was no response to therapy (HR = 18.4; P = 0.018). Of all Croatian patients who underwent LT, 3.8% had PBC, with the survival rate at 5 years after LT of 93.4%. ----- Conclusion: This study gives pioneer insights into the epidemiological and clinical data on PBC in Croatia, thus complementing the PBC map of Southeast Europe.

The aim of the study was to explore (a) prevalence and grade of nonalcoholic fatty liver (NAFL) among outpatients referred for abdominal ultrasound (US) examination and (b) relationship between the presence and severity of liver steatosis and metabolic syndrome (MS). This was a retrospective analysis of patients without history of liver disease examined by abdominal US in the University hospital setting. US was used to detect and semiquantitatively grade (0-3) liver steatosis. Data on patients’ age, gender, body mass index (BMI), impaired glucose metabolism (IGM), atherogenic dyslipidaemia (AD), raised blood pressure (RBP), transaminases, and platelet counts were obtained from medical records. MS was defined as having at least 3 of the following components: obesity, IGM, AD, and RBP. Of the 631 patients (median age 60 years, median BMI 27.4 kg/m2, and 57.4% females) 71.5% were overweight and 48.5% had NAFL. In the subgroup of 159 patients with available data on the components of MS, patients with higher US grade of steatosis had significantly higher BMI and increased prevalence of obesity, IGM, AD, RBP, and accordingly more frequently had MS, whereas they did not differ in terms of age and gender. NAFL was independently associated with the risk of having MS in a multivariate model adjusted for age, gender, BMI, and IGM. The grade of liver steatosis did not correlate with the presence of liver fibrosis. We demonstrated worrisome prevalence of obesity and NAFL in the outpatient population from our geographic region. NAFL is independently associated with the risk of having MS implying worse prognosis.

PURPOSE: To investigate (1) diagnostic performance of transabdominal color doppler ultrasound (US) and endoscopic ultrasound (EUS) for detection and sub-classification of common bile duct varices (CBDV) in patients with portal vein thrombosis (PVT), and (2) clinical significance and natural history of CBDV subtypes. PATIENTS AND METHODS: During a 4-year period, 56 patients with PVT underwent US and EUS for the presence and subtypes of CBDV. Natural history was analyzed for patients who attended control visits. RESULTS: CBDV were diagnosed in 57 and 59 % of patients with US and EUS, respectively. In 19 % of patients, EUS revealed different CBDV subtypes than previously seen by US. The most common were paracholedochal (PCV), while the least common were epicholedochal (ECV) and Submucosal varices (SMV). Nine patients had obstructive jaundice and underwent ERCP which was complicated by hemobilia in two patients with SMV. Among eight patients who underwent control EUS (median follow-up 60 months), the form of CBDV remained unchanged. Two patients bled from esophageal varices, both with ECV. CONCLUSION: While abdominal US and EUS are equally sensitive for detection of CBDV, EUS allows more precise determination of CBDV subtype. Patients with SMV might be at increased risk of bleeding upon ERCP.