Assessment of clinically significant portal hypertension by two-dimensional shear wave elastography.

BACKGROUND AND AIMS: To evaluate two-dimensional shear wave elastography (2DSWE) in parallel with transient elastography (TE) for diagnosing clinically significant portal hypertension (CSPH) and high-risk varices (HRV) in patients with chronic liver disease. PATIENTS AND METHODS: Consecutive patients with suspicion of compensated advanced chronic liver disease (cACLD) [liver stiffness measurement (LSM) ≥ 10 kPa by TE, or morphological signs suggestive of cACLD on imaging], with no history of liver decompensation, underwent hepatic venous pressure gradient (HVPG) measurement, transjugular liver biopsy and esophagogastroduodenoscopy, which served as the reference methods for diagnosing CSPH, cACLD and HRV. All patients underwent LSM and spleen stiffness measurements (SSM) by 2DSWE and TE. RESULTS: Seventy-six (76) patients were included (78% men, mean age 62 years, body mass index 28.3 kg/m2 , 36.8% alcoholic, 30.3% non-alcoholic fatty liver disease, 14.5% viral hepatitis). Of them, 80.3%, 69.7%, 52.6% and 22.4% had cACLD, cirrhosis, CSPH and HRV respectively. LSM performed better than SSM in diagnosing CSPH and HRV. For CSPH, AUROCs (0.926 vs. 0.866), optimal cut-offs (20.1 vs. 20.2 kPa) and sensitivity/specificity (80.5%/94.3% vs. 77.5% /86.1%) were comparable for 2DSWE and TE. Ruling-out of CSPH by 2DSWE (LSM at cut-off with ≥90% sensitivity (13.5 kPa) and platelets ≥ 150 x 109 /L) performed comparably to TE, with 1/24 cases falsely classified as negative. For HRV, AUROCs were similar (0.875 2DSWE, 0.851 TE) with similar optimal LSM cut-offs enabling 100% sensitivity and ruling-out HRV. CONCLUSION: Liver stiffness measurement by 2DSWE appears to perform equally well as TE for diagnosing CSPH and ruling-out HRV in compensated chronic liver disease.

Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: From Epidemiology to Diagnostic Approach.

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.

FibroScan-AST Score Predicts 30-Day Mortality or Need for Mechanical Ventilation among Patients Hospitalized with COVID-19.

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 > 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.

Prognostic Factors in Primary Biliary Cholangitis: A Retrospective Study of Joint Slovak and Croatian Cohort of 249 Patients.

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.

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

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

Comparison of prognostic scores for alcoholic hepatitis: a retrospective study.

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, P<0.0001) and after seven days of hospitalization (cut-off >8, AUC 0.835 95% CI 0.716-0.918, P<0.0001). Modified DF was able to predict the 28- and 90-day mortality only when calculated after seven days of hospitalization. CONCLUSION: There is a need for better prognostic indicators for patients with AH.

Infection as a predictor of mortality in decompensated liver cirrhosis: exploring the relationship to severity of liver failure.

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.

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

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

Epidemiological and clinical features of primary biliary cholangitis in two Croatian regions: a retrospective study.

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 100000 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.

Albi Score as a Predictor of Survival in Patients with Compensated Cirrhosis Resected for Hepatocellular Carcinoma: Exploratory Evaluation in Relationship to Palbi and Meld Liver Function Scores.

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 infiltration. 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 stratified for age, cirrhosis etiology, presence of esophageal varices, hepatocellular carcinoma stage, microvascular invasion, histologic differentiation, and resection margins. We identified 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 significant predictive capabilities for survival in patients with compensated cirrhosis resected for hepatocellular carcinoma.

Hepatitis C is now curable, but what happens with cirrhosis and portal hypertension afterwards?

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.

Non-invasive diagnosis of portal hypertension in cirrhosis using ultrasound based elastography.

Liver stiffness measurement (LSM) by ultrasound-based elastography may be used to non-invasively discriminate between the stages of liver fibrosis, rule out cirrhosis and follow its evolution, including the prediction of the presence of oesophageal varices. The same is possible in order to diagnose clinically significant portal hypertension, referring primarilyto transient elastography and LSM values ≥20-25 kPa. The same approach may be used to reliably rule out the presence ofoesophageal varices (LSM <20 kPa + platelets >150x109/L). These recommendations refer primarily to patients with viral aetiology of chronic liver disease (hepatitis C), while additional studies are required for other aetiologies. While spleen stiffness measurement (SSM) also poses a logical choice in this indication, controversial results have nevertheless been published on this issue. It should be emphasized, however, that more recent data indicate that this parameter should be included in the diagnostic algorithm for portal hypertension, if not as the sole then as a part of a sequential algorithm, combined with LSM. Until now, transient elastography has been most extensively studied and founded on scientific evidence, although the results of other ultrasound-based elastography techniques demonstrate the same trend for the non-invasive assessment of portal hypertension.

The prevalence of diabetes mellitus and abnormal lipid status among Croatian hospitalized coronary heart disease patients.

The aim of this article was to investigate the prevalence of diabetes mellitus and abnormal lipid status with selected anthropometric variables in a sample of hospitalized coronary heart disease (CHD) patients in Croatia (N = 1,298). Prevalence of diabetes mellitus was 31.6% (statistically significantly more frequent in women, 35.7% vs. 30.0%), while prevalences of increased total cholesterol were 72.0%, decreased HDL-cholesterol 42.6% (statistically significantly more frequent in women, 50.2% vs. 39.6%), increased LDL-cholesterol 72.3% and increased triglycerides 51.5%. Reported data on prevalences of diabetes mellitus can be somewhat reassuring (a decrease in its prevalence compared to data from 2006, but they still signal a situation which is a lot worse than in 2002 and 2003); the trend of rising prevalences of dyslipidaemic cardiovascular risk factors must be a cause for an alarm, furthermore as today's preventive and treatment measures in cardiology, both primary and secondary, are strongly focused on dyslipidaemias.