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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 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.

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.

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.

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.

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: 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.

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 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.

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.

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.

Introduction Despite some new treatment possibilities, the improvement in survival rate for hepatocellular carcinoma (HCC) patients is still poor due to late diagnosis. The aim of this study was to investigate the diagnostic sensitivity and specificity of protein induced by vitamin K absence or antagonist-II (PIVKAII), Glypican-3 (GP3), Cystatin B (CSTB), squamous cell carcinoma antigen 1 (SCCA1) and hepatocyte growth factor (HGF) as potential tumour markers for HCC in patients with alcoholic liver cirrhosis (ALC) using imaging techniques (MSCT and MRI) as reference standards. Patients and methods Eighty-three participants were included: 20 healthy volunteers, 31 patients with ALC and 32 patients with HCC. Peripheral blood sampling was performed for each participant, and serum concentrations of PIVKAII, GP3, CSTB, SCCA1 and HGF were determined using commercial ELISA kits. Results Only serum concentrations of PIVKAII were significantly higher in HCC patients as compared with ALC and healthy controls (cut-off: 2.06 µg/L; AUC: 0.903), whereas individual diagnostic performance of other individual compounds was inadequate. The ‘best’ combination of tumour markers in our study includes all tested markers with AUC of 0.967. Conclusion While novel diagnostic tumour markers are urgently needed, the examined potential tumour markers, with the exception of PIVKAII seem to be inadequate for diagnosing HCC in ALC. Furthermore, probably the future is in finding the best optimal combination of tumour markers for diagnosing HCC based on cost-effectiveness.

Background: Data on the efficacy of particular therapeutic protocols of interferon-α (IFN-α) treatment for chronic hepatitis C in patients on hemodialysis (HD) vary. Aim: To compare the efficacy of two different therapeutic protocols for HD patients. Patients and Methods: 15 hepatitis C virus (HCV)-positive patients on chronic HD at two dialysis centers: 8 patients treated with IFN-α 3 × 3 MU/week s.c. for 6 months (group A), and 7 patients treated with IFN-α 3 × 5 MU/week for 3 months, then 1 × 5 MU/week for another 3 months (group B). End of treatment response (ETR) and sustained virologic response (SVR) were evaluated by HCV-RNA determination. There was no statistically significant difference between the two patient groups according to age, sex, duration of HD and HCV infection. Results: ETR was 87.5% (7/8) in group A and 28.5% (2/7) in group B, being statistically significant (p < 0.05). Although better SVR [50% (4/8) vs. 28.5% (2/7)] and lower drop-out rate [0% (0/8) vs. 28.5% (2/7)] were achieved in group A compared to group B, these differences did not reach statistical significance (p > 0.05). Conclusion: Therapy with IFN-α 3 × 3 MU/week s.c. for 6 months seems to be more appropriate for treatment of hepatitis C in HD patients, mostly due to better tolerability, i.e. lower drop-out rate. These differences could be attributed to different pharmacokinetic properties of the particular therapy protocol.

Objectives To investigate the performance of real-time 2D shear wave elastography (RT 2D-SWE) for non-invasive staging of liver disease in patients with chronic viral hepatitis (CVH). Materials and methods Naive CVH patients underwent liver (LS) and spleen stiffness (SS) measurements by an intercostal approach. Patients with ALT >3× upper limit of normal, cholestasis as revealed by dilated intrahepatic biliary tree, and liver congestion were excluded. Results were expressed in kPa and compared to histological stage (Ishak) of liver fibrosis (LF). Patients with decompensated liver cirrhosis (LC) were diagnosed using standard clinical, ultrasound, and endoscopic criteria. Results Of 123 patients, LS was successfully measured in 79.7 % and SS in 53.7 %. LS accurately differentiated between liver disease stages, with cut-off values of 8.1 (AUC 0.991) for F ≥ 3, 10.8 kPa (AUC 0.954) for F ≥ 5, and 27 kPa (AUC 0.961) for decompensated LC. SS was significantly different between non- cirrhotic stages (F0–4) and LC (cut-off 24 kPa ; AUC 0.821). While both LS and SS increased with liver disease progression, the difference between them decreased, as reflected by the stiffness ratio index. Conclusions RT 2D-SWE can accurately differentiate between the stages of LF, and can distinguish LF from LC and compensated from decompensated LC. Key Points • RT 2D-SWE is an accurate method for assessment of liver fibrosis. • RT 2D-SWE is applicable in 80 % of patients with chronic viral hepatitis. • RT 2D-SWE accurately differentiates compensated from decompensated liver cirrhosis. • Both liver and spleen stiffness increase with progression of liver fibrosis. • In cirrhosis, the difference between liver and spleen stiffness decreases.

A case of mesalazine-induced acute interstitial nephritis (AIN) in a 41-year-old patient with ulcerative colitis (UC) is reported here. Clinical symptoms such as fever and arthralgia, and laboratory findings such as eosinophilia and renal failure suggested AIN, which was confirmed by biopsy. With withdrawal of mesalazine and intravenous methylprednisolone the patient's renal function was recovered. It is observed that early discontinuation of mesalazine is associated with amelioration of interstitial nephritis in most patients, so the recommendation is that patients receiving mesalazine should undergo routine monitoring of renal function. Delayed diagnosis may lead to permanent renal function impairment.

Endoscopic ultrasound (EUS) is continuously stepping into the therapeutic arena, simultaneously evolving in different directions, such as the management of pancreatic and biliary diseases, celiac neurolysis, delivering local intratumoral therapy, and EUS-guided endosurgery. EUS-guided vascular procedures are also challenging, considering the variety of vascular pathology, proximity of the vascular structures to the GI tract wall, high resolution, and real-time guidance offering an attractive access route and precise delivery of the intervention. The literature on vascular therapeutic EUS demonstrates techniques for the management of upper GI variceal and nonvariceal bleeding, pseudoaneurysms, and coiling and embolization procedures, as well as the creation of intrahepatic portosystemic shunts. The paucity of studies, diversity of study designs, and the number of animal model studies hamper a systematic approach to the conclusion and decision making important to clinicians and healthcare policy makers. Nevertheless, theoretical benefits and findings up to date concerning technical feasibility, efficacy, and safety of the procedures drive further research and development in this rather young therapeutic arena.

There is insufficient information on the effects of chemotherapy protocols for Hodgkin's disease (HD) and the course of coexisting hepatitis C virus (HCV) infection. A single literature case reported a patient with HD who developed fulminant hepatitis and hepatic coma after receiving chemotherapy. The case described here is of a female patient previously exposed to prolonged war stress, complicated by intravenous drug abuse and chronic hepatitis C. One year after diagnosis of HCV infection she was diagnosed with HD (nodular sclerosis type II, clinical stage IIIB). The patient received six cycles of ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) resulting in complete remission of HD. There was no hepatitis flare either during or after chemotherapy. In conclusion, there were no adverse effects of the ABVD regimen on the course of HCV infection in this patient who was successfully treated for HD. Because concurrent HCV infection and HD is extremely rare, we discuss here the possibility of the synergistic contribution of chronic war stress and hepatitis C infection in the pathogenesis of HD.

PURPOSE: To evaluate acoustic radiation force impulse imaging (ARFI) of the liver and spleen as a new method for the noninvasive assessment of liver fibrosis (LF). MATERIALS AND METHODS: Three groups of 58 examinees were studied: (A) 20 healthy volunteers; (B) 18 patients with chronic viral hepatitis (CVH) B or C having liver fibrosis stages F 1 - 4 (assessed by liver biopsy; Ishak classification); and (C) 20 patients with liver cirrhosis (LC). All participants were examined using the Siemens ACUSON S 2000 Ultrasound Virtual Touch Tissue Quantification™ system. Ten measurements were performed on both liver lobes and three measurements on the spleen, and the obtained mean values (shear wave velocities [SWV] expressed in m/s) were compared between the groups. In 20 patients the splenic artery pulsatility index (SAPI) was also measured and correlated to the liver and splenic ARFI and histological stage of LF. RESULTS: Hepatic ARFI measurements demonstrated a significant correlation to LB results (Spearman's ρ = 0.766; ρ < 0.001) and SWV cut-off values of 1.3 (AUC 0.96) and 1.86 (AUC 0.99) could reliably differentiate between healthy (A) and non-cirrhotic CVH (B), as well as between non-cirrhotic CVH (B) and LC (C). Splenic SWV cut-off value of 2.73 (AUC 0.82) could differentiate between the patients with LC and non-cirrhotic CVH. A significant correlation was also observed between the SAPI and liver ARFI results (ρ = 0.56; p = 0.013). CONCLUSION: The hepatic and splenic SWV measured by ARFI increase with the LF stage, and the hepatic SWV correlate well with SAPI. This new technology enables simultaneous morphological, Doppler and elastometric examinations and might improve the accuracy of noninvasive liver fibrosis assessment.

Objective: The aim of this study was to determine the prevalence and risk factors for peptic ulcer disease (PUD) in dyspeptic patients with ischemic heart disease (IHD), and to assess whether the healing of PUD before coronary artery bypass grafting (CABG) could reduce the need for urgent postoperative endoscopy. Patients and Methods: A series of 894 patients referred to Dubrava University Hospital in Zagreb for elective CABG during the period from May 1998 until April 2001 was prospectively analysed. Dyspepsia was assessed by a questionnaire, PUD by upper gastrointestinal endoscopy, and H. pylori status by histology/Giemsa staining and the rapid urease test. The need for urgent postoperative endoscopy (hematemesis and/or melena, sudden onset of anemia or unexplained epigastric pain) was compared between the prospective study group of 894 patients and a series of 463 patients referred for CABG to Dubrava University Hospital during the period from January 1997 until April 1998. Results: Gastroduodenal dyspepsia predominated in 184 (20.6 %) patients, 142 (77.2 %) of them with Helicobacter (H.) pylori infection and 69 (37.5 %) with verified PUD. Univariate analysis indicated the increased risk of multiple PUD to be related to a previous diagnosis of PUD (OR 3.61, 95 % CI 1.32 - 9.82), H. pylori infection (OR 18.86, 95 % CI 2.31 - 153.98), use of aspirin (OR 5.70 ; 95 % CI 1.80 - 18.03) and left coronary artery occlusions (3.10, 95 % CI 1.00 - 9.59). Multivariate analysis pointed to H. pylori infection (OR 16.30, 95 % CI 1.57 - 168.53) and left coronary artery occlusions (OR 4.84, 95 % CI 1.05 - 22.30) as independent risk factors for multiple PUD. The OR for urgent postoperative endoscopy due to a major gastrointestinal event was 9.9 (95 % CI 2.2 - 45.1) and the OR for active peptic ulcer with stigmata of recent bleeding was 6.9 (95 % CI 1.4 - 33.1) in the group of patients with IHD who were not submitted to evaluation for dyspepsia prior to elective heart surgery. Conclusions: In areas with a high prevalence of H. pylori infection, endoscopy and a “ search and treat” strategy for IHD patients with dyspepsia before elective cardiac surgery should significantly reduce the need for urgent postoperative endoscopy due to major gastrointestinal events.

Dear Editor, Colorectal cancer (CRC) is one of the most common cancer types in the world, ranked second in developed countries for both genders, with the incidence of around 70–80 per population of 100,000. CRC disseminates most frequently to liver, lung, and bones, whereas it is rather rare in other organs. The incidence of colorectal adenocarcinoma dissemination to the leptomeninges is not estimated and seems to be quite rare. We report a case of a woman with CRC and the disease dissemination to the leptomeninges as the first and only dissemination site. A 61-year-old woman presented to the infectious diseases emergency room with a one-month history of fatigue, fever, photophobia, and mild headache that progressed to severe headache and vertigo. All of these symptoms appeared shortly after a mild conjunctivitis on both eyes that was treated with tobramycin eye-drops. The patient also emphasized a 1-year history of strabismus of the right eye and substantial weight loss of about 12 kg in a period of several months. She had no history of malignancies or any other serious diseases. Fifteen years ago, she had cataract surgery with a plastic lens implemented in her left eye. Physical examination, except for nonparalytic convergent strabismus of the right eye, was unremarkable with no clinical signs of meningitis. Body temperature was 38.0°C. Upon admission to the infectious diseases ward, a lumbar puncture was performed. The cerebrospinal fluid (CSF) analysis showed hypercellular sterile CSF with predominantly adenocarcinoma cells of unknown origin with elevated total protein level (64.5 g/dL) and low glucose level (1.9 mmol/L—33% of the blood level). The contrast-enhanced computed tomography (CECT) of the brain, made in order to enlighten this finding, did not find any pathological substrate except mild maxillary sinusitis on the left. Computed tomography (CT) of the abdomen was performed thereafter, and a large tumor mass in the ascending colon was found, though the patient had no symptoms or clinical signs of gastrointestinal obstruction. No lesions elsewhere in the abdomen were detected. Chest X-ray examination was normal. Thereafter, the patient was referred to the gastroenterology ward. Physical examination on admission to the gastroenterology ward showed moderate pain on deep palpation in the right iliac region and nonparalytic convergent strabismus of the right eye with hypermature cataract of the same eye. Neurological examination revealed no evidence of motor dysfunction or sensory changes including pathologic reflexes, except the aforementioned convergent strabismus, photophobia, and vertigo. The complete blood count revealed mild anemia with hemoglobin concentration of 114 g/L. Laboratory serum examination results showed high cholesterol (7.56 mmol/L) and triglyceride (2.84 mmol/L) level, increased gamma glutamyl-transpeptidase (90 U/L) and low concentration of iron (2.5 μmol/L). Blood coagulation was also slightly impaired with prothrombin time of 0.93 INR, fibrinogen of 5.8 g/L, and prolonged fibrinolysis. Additionally, C-reactive protein of 31.1 mg/L was detected. Tumor marker carbohydrate antigen 19-9 was highly increased (>1,000 kIU/L) with carcinoembryonic Int J Colorectal Dis (2009) 24:355–356 DOI 10.1007/s00384-008-0560-7