This study evaluates the predictive value of the lactate/albumin ratio (LAR) for all-cause mortality in cirrhosis patients.

Retrospective observational study.

Intensive care unit (ICU).

626 first-time ICU-admitted cirrhosis patients in the USA (MIMIC-IV v2.2).

None.

LAR index, 28-day, and 90-day all-cause mortality.

Of 626 patients (60.86% male), 27.80% and 39.14% died within 28 and 90 days, respectively. Multivariate Cox analysis showed a significant association between higher LAR and mortality. Adjusted for confounders, elevated LAR increased the 28-day mortality risk [HR: 1.31 (1.21-1.42), P < 0.001]. A restricted cubic spline analysis revealed non-linear relationships between LAR and mortality. For 28-day mortality, the inflection point was 1.583: below this, HR was 2.29 (95% CI: 1.61-3.27, P < 0.001); above, HR was 1.16 (95% CI: 1.02-1.31, P = 0.021; P = 0.002). For 90-day mortality, the inflection point was 1.423: below, HR was 1.60 (95% CI: 1.04-2.47, P = 0.033); above, HR was 0.94 (95% CI: 0.75-1.16, P = 0.542; P = 0.012).

LAR predicts 28-day and 90-day mortality with a segmented effect. An LAR ≥1.583 signals high 28-day mortality risk, necessitating intensified monitoring and potential ICU admission. For 90-day mortality, LAR near 1.423 serves as an early warning for high-risk patients and guides interventions. Continuous LAR monitoring aids management, but prospective studies are needed to confirm clinical utility.

Liver biopsy is a crucial aspect of interventional radiology and plays a significant role in the management of hepatobiliary diseases. Radiologists commonly perform two major image-guided liver biopsy techniques: percutaneous and transjugular approaches. It is essential for radiologists to understand the role of liver biopsy in diagnosing and treating hepatobiliary conditions, the procedural details involved, and how to manage potential complications. This article reviews the indications, contraindications, techniques, and efficacy of image-guided liver biopsy, with a focus on both percutaneous and transjugular methods.

Early detection of esophageal varices (EV) before the first attack of bleeding is crucial for primary prophylaxis. The current work aims to investigate the use of a combination of FibroScan and platelet count as noninvasive means to identify EV in patients with compensated cirrhosis.

Sixty-two patients with compensated hepatitis C virus (HCV)-related cirrhosis were divided into two groups with and without EV. All patients were exposed to complete history, physical examination, laboratory, and endoscopic evaluation. FibroScan was performed for all patients, and the two groups were compared.

A statistically significant higher mean liver stiffness measurement (LSM) (KPa), lower mean platelet count to splenic diameter ratio (PSR), and higher mean fibrosis-4 (FIB4) score were noticed in those with EV with P < 0.0005. A cutoff value of ≥23.1 for LSM, ≥3.71 for FIB4, and ≥130 mm for splenic diameter have a sensitivity of 94%, 97%, and 97% and a specificity of 81%, 81%, and 68%, respectively, in the detection of varices. Platelet count of ≥112,500 (×103/dl) and of ≥771.33 for PSR have a sensitivity of 84% and 77% and a specificity of 87% and 90%, respectively, to rule out the presence of varices. LSM, FIB4 score, and splenic diameter are predictors of the presence of varices where platelet count and PSR are negative predictors.

The combination of LSM by transient elastography (TE), PSR, or platelet count can be used to detect a relevant category of patients with compensated cirrhosis who have a very low possibility of EV where endoscopy can be avoided.

A variety of liver disorders are associated with characteristic histopathological findings that help in their diagnosis and treatment. However, percutaneous liver biopsy (PLB) is prone to limitations and complications. We evaluated all PLBs done in our hospital in a 13-year period, aiming to assess PLB's utility and complications.

All PLBs conducted in an internal medicine department of a tertiary university hospital in Athens, Greece, during a 13-year period were reviewed. Recorded data included demographic characteristics, laboratory results acquired on biopsy day, indication for liver biopsy, and occurrence of side effects. All patients were followed for 1 month post-hospital discharge for possible PLB-related complications.

A total of 261 patients underwent PLB during the study period. The commonest indication of PLB was investigation of liver mass, followed by transaminasemia. PLB assisted in setting a diagnosis in 218 patients and was unhelpful in only 43, in 14 of them due to inadequate or inappropriate biopsy specimen. Complications attributable to PLB were rare, with 10 patients exhibiting pain, either at biopsy site or in the right shoulder, and 3 having bleeding episodes; no deaths were noted.

Our study shows that PLB is still a powerful diagnostic tool in everyday practice, provided it is used when indicated.

Liver cirrhosis in children is a rare disease with multifactorial causes that are distinct from those in adults. Underlying reasons include cholestatic, viral, autoimmune, hereditary, metabolic and cardiac disorders. Early detection of fibrosis is important as clinical stabilization or even reversal of fibrosis can be achieved in some disorders with adequate treatment. This article focuses on the longitudinal evaluation of children with chronic liver disease with noninvasive imaging tools, which play an important role in detecting cirrhosis, defining underlying causes, grading fibrosis and monitoring patients during follow-up. Ultrasound is the primary imaging modality and it is used in a multiparametric fashion. Magnetic resonance imaging and computed tomography are usually applied second line for refined tissue characterization, clarification of nodular lesions and full delineation of abdominal vessels, including portosystemic communications.

In this preliminary study, our aim was to assess the utility of quantitative native-T₁ (T₁-pre), iron-corrected T₁ (cT₁) of the liver/spleen and T₁ mapping of the liver obtained during hepatobiliary phase (T₁-HBP) post-gadoxetate disodium, compared to spleen size/volume and APRI (aspartate aminotransferase-to-platelet ratio index) for noninvasive diagnosis of clinically significant portal hypertension [CSPH, defined as hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg].

Forty-nine patients (M/F: 27/22, mean age 53y) with chronic liver disease, HVPG measurement and MRI were included. Breath-held T₁ and cT₁ measurements were obtained using an inversion recovery Look-Locker sequence and a T2* corrected modified Look-Locker sequence, respectively. Liver T₁-pre (n = 49), spleen T₁ (obtained pre-contrast, n = 47), liver and spleen cT₁ (both obtained pre-contrast, n = 30), liver T₁-HBP (obtained 20 min post gadoxetate disodium injection, n = 36) and liver T₁ uptake (ΔT₁, n = 36) were measured. Spleen size/volume and APRI were also obtained. Spearman correlation coefficients were used to assess the correlation between each of liver/spleen T₁/cT₁ parameters, spleen size/volume and APRI with HVPG. ROC analysis was performed to determine the performance of measured parameters for diagnosis of CSPH.

There were 12/49 (24%) patients with CSPH. Liver T₁-pre (r = 0.287, p = 0.045), liver T₁-HBP (r = 0.543, p = 0.001), liver ΔT₁ (r =  - 0.437, p = 0.008), spleen T₁ (r = 0.311, p = 0.033) and APRI (r = 0.394, p = 0.005) were all significantly correlated with HVPG, while liver cT₁, spleen cT₁ and spleen size/volume were not. The highest AUCs for the diagnosis of CSPH were achieved with liver T₁-HBP, liver ΔT₁ and spleen T₁: 0.881 (95%CI 0.76-1.0, p = 0.001), 0.852 (0.72-0.98, p = 0.002) and 0.781 (0.60-0.95, p = 0.004), respectively.

Our preliminary results demonstrate the potential of liver T₁ mapping obtained during HBP post gadoxetate disodium for the diagnosis of CSPH. These results require further validation.

The value of noninvasive tools in the diagnosis of autoimmune hepatitis (AIH)-related cirrhosis and the prediction of clinical outcomes is largely unknown. We sought to evaluate (1) the utility of liver stiffness measurement (LSM) in the diagnosis of cirrhosis and (2) the performance of the Sixth Baveno Consensus on Portal Hypertension (Baveno VI), expanded Baveno VI, and the ANTICIPATE models in predicting the absence of varices needing treatment (VNT). A multicenter cohort of 132 patients with AIH-related cirrhosis was retrospectively analyzed. LSM and endoscopies performed at the time of cirrhosis diagnosis were recorded. Most of the patients were female (66%), with a median age of 54 years. Only 33%-49% of patients had a LSM above the cutoff points described for the diagnosis of AIH-related cirrhosis (12.5, 14, and 16 kPa). Patients with portal hypertension (PHT) had significantly higher LSM than those without PHT (15.7 vs. 11.7 kPa; P = 0.001), but 39%-52% of patients with PHT still had LSM below these limits. The time since AIH diagnosis negatively correlated with LSM, with longer time being significantly associated with a lower proportion of patients with LSM above these cutoffs. VNT was present in 12 endoscopies. The use of the Baveno VI, expanded Baveno VI criteria, and the ANTICIPATE model would have saved 46%-63% of endoscopies, but the latter underpredicted the risk of VNT. Conclusions: LSM cutoff points do not have a good discriminative capacity for the diagnosis of AIH-related cirrhosis, especially long-term after treatment initiation. Noninvasive tools are helpful to triage patients for endoscopy.

Patients with liver cirrhosis are fragile and present specific clinical hallmarks. When undergoing to gastrointestinal (GI) endoscopy, these subjects require an individual pre evaluation, taking into account: Level of haemostasis impairment, the individual risk of infection, the impact of sedation on hepatic encephalopathy and other factors. The overall assessment of liver function, employing common scoring systems, should be also assessed in the preprocedural phase. Beside some common general problems, regarding GI endoscopy in cirrhotic subjects, also specific issues are present for some frequent indications or procedures. For instance, despite an increased incidence of adenomas in cirrhosis, colon cancer screening remains suboptimal in subjects with this disease. Several studies in fact demonstrated liver cirrhosis as a negative factor for an adequate colon cleansing before colonoscopy. On the other hand, also the routine assessment of gastroesophageal varices during upper GI endoscopy presents some concern, since important inter-observer variability or incomplete description of endoscopic findings has been reported in some studies. In this review we discussed in details the most relevant issues that may be considered while performing general GI endoscopic practice, in patient with cirrhosis. For most of these issues there are no guidelines or clear indications. Moreover until now, few studies focused on these aspects. We believe that targeting these issues with corrective measures may be helpful to develop a tailored endoscopic approach for cirrhosis, in the future.

Endoscopy is the gold standard investigation for diagnosis of gastroesophageal varices (GOVs), yet it is invasive, associated with complications. Many noninvasive parameters were investigated to predict the presence of GOVs. The current study investigated gallbladder wall thickening (GBWT) measurement as a noninvasive predictor of GOVs in posthepatitic cirrhotic patients with portal hypertension.

In this cross-sectional study, 105 cirrhotic patients were divided into, group I and II according to the presence or absence of GOVs, respectively. Group I subdivided into, groups A and B according to the grade of GOVs either nonadvanced (grades I and II) or advanced (grades III and IV), respectively. Complete history taking, full clinical examination, full investigations, upper endoscopy and abdominal ultrasonography were performed to examine all patients.

Both groups were comparable in their baseline characteristics except for AST to Platelet Ratio Index and Fibrosis-4 scores, which were significantly higher in group I. GBWT, portal vein diameter and spleen length were significantly associated not only with GOVs but also with its advanced grades. GBWT at a cutoff level >3.1 mm can predict the presence of GOVs with 54.29% sensitivity, 97.14% specificity, 97.4% positive predictive value (PPV), 51.5% negative predictive value (NPV) and 68.5% accuracy. GBWT can predict advanced grades of GOVs at a cutoff level >3.5 mm, with 45% sensitivity, 90% specificity, 64.3% PPV, 80.4% NPV and 77.1% accuracy.

GBWT was associated with the presence of GOVs, and with advanced GOVs in posthepatitis cirrhotic patients with portal hypertension.

This study aimed to determine the prognostic role of the categorized hemodynamic stage (HS) based on the hepatic venous pressure gradient (HVPG) in patients with portal hypertension.

Of 1,025 cirrhotic patients who underwent HVPG measurement, data on 572 non-critically-ill patients were collected retrospectively between 2008 and 2013. The following two HS categorizations were used: HS-1 (6-9, 10-12, 13-16, 17-20, and > 20 mmHg; designated as groups 1-5, respectively) and HS-2 (6-12, 13-20, and > 20 mmHg). Clinical characteristics, mortality rates, and prognostic predictors were analyzed according to the categorized HS.

During the mean follow-up period of 25 months, 86 (15.0%) patients died. The numbers of deaths in HS-1 groups were 7 (6.3%), 7 (6.9%), 30 (18.0%), 20 (15.6%), and 22 (34.4%), respectively (P < 0.001). However, the traditional HVPG cutoffs of 10 and 16 mmHg did not improve the discrimination of mortality. In contrast, the mortality rates did differ significantly between the three HS-2 groups (P < 0.05). In the multivariate analysis, all models revealed that HS-2 was a common prognostic factor in predicting mortality. The mortality rates increased significantly according to HS-2 in patients with hypoalbuminemia (HVPG, 13-20 mmHg; hazard ratio [HR], 2.54 and HVPG > 20 mmHg; HR, 5.45) and intermediate model for end-stage liver disease (MELD) score (HVPG, 13-20 mmHg; HR, 3.86 and HVPG > 20 mmHg; HR, 8.77; P < 0.05).

Categorizing HVPG values according to HS-2 is a useful prognostic modality in patients with portal hypertension and can play an independent role in predicting the prognosis in patients with hypoalbuminemia and an intermediate MELD score.

Both liver stiffness (LS) and spleen stiffness (SS) are widely used to non-invasively assess liver fibrosis and portal hypertension, respectively. We aimed to identify the impact of disease etiology, namely the localization of inflammation (portal vs. lobular), on the SS/LS ratio.

In this multicenter study, LS and SS were prospectively assessed in 411 patients with alcohol-related liver disease (ALD) or hepatitis C virus (HCV) using FibroScan® (Echosens, Paris); changes in these parameters were also studied in response to treatment (alcohol withdrawal, HCV therapy). LS and spleen length (SL) were further analyzed in a retrospective cohort of 449 patients with long-term data on decompensation/death.

Both, SS and SL were significantly higher in HCV compared to ALD (42.0 vs. 32.6 kPa, p≪0.0001, 15.6 vs. 11.9 cm, p≪0.0001) despite a lower mean LS in HCV. Consequently, the SS to LS ratio and the SL to LS ratio were significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, p≪0.0001) through all fibrosis stages. Notably, SL linearly increased with SS and the relation between SS and SL was identical in HCV and ALD. In contrast, livers were much larger in ALD at comparable LS. After treatment, LS significantly decreased in both diseases without significant changes to the SS/LS ratio. In the prognostic cohort, patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%); liver failure was the major cause of death (p≪0.01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (p≪0.001).

Both SS/LS and SL/LS ratios are significantly higher in patients with portal HCV compared to lobular ALD. Thus, combined LS and SS or SL measurements provide additional information about disease etiology and disease-specific complications.

Herein, we show that patients with hepatitis C virus infection (HCV) have higher spleen stiffness and portal pressure than patients with alcohol-related liver disease (ALD), within the same fibrosis stage and matched to liver stiffness. Thus, the spleen stiffness to liver stiffness ratio is significantly higher in patients with HCV compared to ALD. Additionally, patients with HCV more commonly progress to portal hypertension-related complications (e.g. variceal bleeding), while patients with ALD more commonly progress to liver failure (e.g. jaundice). The spleen stiffness to liver stiffness ratio is a useful tool to confirm disease etiology and predict disease-specific complications.

This study aimed at the participation of lncRNA H19, endothelial NADPH oxidases (NOX4) and miR-148b-3p in hypoxia stress in human hepatic sinusoidal endothelial cells (HHSEC), and clarifying the relationship among them. The expression of lnc H19, NOX4 and miR-148b-3p in cirrhotic patients and hypoxic HHSEC were measured by RT-PCR. The nitric oxide and hydrogen peroxide content in HHSEC were determined using ultraviolet chromatometry. The protein levels of NOX4, endothelial NOS (eNOS) and phosphorylated eNOS (p-eNOS) were measured via western blotting. The interaction between NOX4 promoter and lnc H19/miR-148b-3p was measured by dual-luciferase reporter gene detection system. The present results indicated that the expressions of NOX4 mRNA and lnc H19 were increased but miR-148b-3p was decreased in both cirrhotic patients and hypoxic HHSEC. Further, hypoxia induced the up-regulation of hydrogen peroxide and the down-regulation of eNOS/NO signaling in HHSEC. And these symptoms were ameliorated by lnc H19 shRNA and miR-148b-3p mimics. But the beneficial effects of lnc H19 shRNA and miR-148b-3p mimics were further abolished by miR-148b-3p inhibitor and NOX4 over-expression, respectively. In addition, NOX4 was a direct, negatively regulated target of miR-148b-3p, and miR-148b-3p was negatively regulated by lnc H19. Collectively, lnc H19 is a negatively regulator of microRNA-148b-3p, and participate in hypoxia stress in HHSEC via positively regulating NOX4 and negatively regulating eNOS/NO signaling.

There is no consensus on screening for high-risk esophageal varices (HRV) in patients with hepatocellular carcinoma (HCC). Here, we aimed to investigate the prevalence and risk factors of HRV in patients with HCC and to assess the combination of albumin-bilirubin grade and platelet count (ALBI-PLT score) for predicting compensated patients who do not need unnecessary endoscopic screening for HRV.

The ALBI-PLT score was calculated by adding the ALBI grade and points for platelet count (1 point if platelet count >150,000/mm³ and 2 points if ≤150,000/mm³). The predictive value of the ALBI-PLT score for HRV was analyzed in 887 compensated patients enrolled from October 2007 to April 2014 (study cohort). This was validated in 215 compensated patients from May 2014 to December 2015 (validation cohort).

In the study cohort, the rates of HRV were 2.9% and 21.1% in compensated HCC patients with an ALBI-PLT score of 2 and >2, respectively. The negative predictive values of the ALBI-PLT score for predicting HRV were 97.1% and 98.1% in the study and validation cohorts, respectively. For compensated patients who did not receive endoscopic screening at the time of HCC diagnosis, the 5-year cumulative variceal hemorrhage rate was lower in patients with an ALBI-PLT score of 2 than in those with an ALBI-PLT score >2 (1.7% vs 9.1%, P = .007).

In patients with HCC with compensated liver function, an ALBI-PLT score of 2 predicted a very low risk of HRV and variceal hemorrhage; therefore, endoscopic screening for esophageal varices is not recommended for these patients.

To test a magnetic resonance (MR) scanning protocol as a noninvasive tool to determine hepatic hemodynamics and to assess the degree of liver fibrosis in an animal model of liver fibrosis and cirrhosis.

Fifty-four male Wistar rats were studied. Thirty-nine received thioacetamide (TAA) in their drinking water for either 12 or 16 weeks. MR measurements were performed using flow-sensitive 2D phase-contrast MRI and a 9.4T preclinical scanner. The following hemodynamic parameters were investigated: portal cross-sectional area, mean portal flow velocity, and portal and aortic flow volume rate. Therefore, rats (n = 46) were divided into three groups: CON (control, n = 13), FIB (fibrosis, n = 25), and CIR (cirrhosis, n = 8). Furthermore, the degree of liver fibrosis was assessed by a self-established MR score and verified by a standardized histological score (n = 48).

Portal and aortic flow parameters could be reliably detected. A significant decrease in portal flow velocity was found in FIB (FIB vs. CON: -21%, P = 0.006 and CIR vs. CON: -17%, P = 0.105) and in portal flow volume rate in FIB and CIR (FIB vs. CON: -20%, P = 0.009 and CIR vs. CON: -25%, P = 0.024). If the histological score is taken as standard, the self-established MR score enabled discrimination between healthy and diseased livers (sensitivity to identify diseased livers: 89% and specificity to identify healthy livers: 100%).

This MR scanning protocol presents a noninvasive tool to determine hepatic hemodynamics in healthy and diseased rats.

2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1526-1534.

This study aimed to evaluate easily available computed tomography (CT)-based parameters for assessing the presence and severity of cirrhosis and predicting complications in Chinese patients with cirrhosis.

CT-based morphological indices were determined in 167 patients with cirrhosis and 244 healthy volunteers. The correlation of morphological indices with Child-Pugh score and cirrhotic complications was analyzed using Spearman's correlation analysis. The area under the receiver operating characteristic curve (AUROC) was used to analyze the diagnostic performance of the indices. Sensitivity and specificity were determined.

Patients with cirrhosis had a lower total liver volume (TLV) and a larger total splenic volume (SV) than healthy individuals. There was a significant difference in the portal venous diameter, splenic venous diameter and portal venous cross-sectional area between the two groups. A low TLV/SV ratio was strongly associated with liver cirrhosis; with a cut-off value of 4.27 for the diagnosis of cirrhosis TLV/SV had a sensitivity of 87.7% and a specificity of 84.9%, and AUROC of 0.921. Further analysis showed that TLV/SV was accurate in discriminating between mild and moderate/severe cirrhosis and could be used for predicting complications of cirrhosis.

The easily available parameters of CT can accurately evaluate the severity of cirrhosis in Chinese patients.

In patients with compensated advanced chronic liver disease (cACLD), the presence of clinically significant portal hypertension (CSPH) and varices needing treatment (VNT) bears prognostic and therapeutic implications. Our aim was to develop noninvasive tests-based risk prediction models to provide a point-of-care risk assessment of cACLD patients. We analyzed 518 patients with cACLD from five centers in Europe/Canada with paired noninvasive tests (liver stiffness measurement [LSM] by transient elastography, platelet count, and spleen diameter with calculation of liver stiffness to spleen/platelet score [LSPS] score and platelet-spleen ratio [PSR]) and endoscopy/hepatic venous pressure gradient measurement. Risk of CSPH, varices, and VNT was modeled with logistic regression. All noninvasive tests reliably identified patients with high risk of CSPH, and LSPS had the highest discrimination. LSPS values above 2.65 were associated with risks of CSPH above 80%. None of the tests identified patients with very low risk of all-size varices, but both LSPS and a model combining TE and platelet count identified patients with very low risk (<5%) risk of VNT, suggesting that they could be used to triage patients requiring screening endoscopy. LSPS values of <1.33 were associated with a <5% risk of VNT, and 26% of patients had values below this threshold. LSM combined with platelet count predicted a risk <5% of VNT in 30% of the patients. Nomograms were developed to facilitate point-of-care risk assessment.

A significant proportion of patients with a very high risk of CSPH, and a population with a very low risk of VNT can be identified with simple, noninvasive tests, suggesting that these can be used to individualize medical care. (Hepatology 2016;64:2173-2184).

As advances in liver disease continue, including the increasing use of liver transplantation, the endoscopist needs to be familiar with the standards of care and potential complications in the management of the cirrhotic population. This includes both elective endoscopic procedures, such as screening colonoscopies and variceal banding, as well as the acutely bleeding cirrhotic patient. Peri-procedural management and standards of care for acute gastrointestinal hemorrhaging of cirrhotic patients will be emphasized. This article will focus on the plethora of data available to highlight the benefits of endoscopic intervention in the care of patients with liver disease and outline the areas of future emphasis.

Development of non-invasive assay for the accurate diagnosis of progressive liver diseases (e.g., fatty liver and hepatocellular carcinoma (HCC)) is of great clinical significance and remains to be a big challenge. Herein, we reported the synthesis of strawberry-like Fe3O4-Au hybrid nanoparticles at room temperature that simultaneously exhibited fluorescence, enhanced X-ray attenuation, and magnetic properties. The results of in vitro fluorescence assay showed that the nanoparticles had significant photo-stability and could avoid the endosome degradation in cells. The in vivo imaging of normal mice demonstrated that the Fe3O4-Au nanoparticles provided 34.61-fold contrast enhancement under magnetic resonance (MR) guidance 15 min post the administration. Computed tomography (CT) measurements showed that the highest Hounsfield Unit (HU) was 174 at 30 min post the injection of Fe3O4-Au nanoparticles. In vivo performance of the Fe3O4-Au nanoparticles was further evaluated in rat models bearing three different liver diseases. For the fatty liver model, nearly homogeneous contrast enhancement was observed under both MR (highest contrast ratio 47.33) and CT (from 19 HU to 72 HU) guidances without the occurrences of focal nodules or dysfunction. For the cirrhotic liver and HCC, pronounced enhancement under MR and CT guidance could be seen in liver parenchyma with highlighted lesions after Fe3O4-Au injection. Furthermore, pathological, hematological and biochemical analysis revealed the absence of acute and chronic toxicity, confirming the biocompatibility of our platform for in vivo applications. Collectively, These Fe3O4-Au nanoparticles showed great promise as a candidate for multi-modality bio-imaging.

The hepatic venous pressure gradient (HVPG) is an important but invasive diagnostic and prognostic marker in cirrhotic patients. The aim of the study was to evaluate a novel biochemical plasma marker of true type V collagen formation (Pro-C5) for describing HVPG.

Ninety-four patients mainly with alcoholic cirrhosis and fourteen liver-healthy controls were included in a retrospective study. Relevant clinical and routine laboratory data and hemodynamics were determined. Plasma Pro-C5 was correlated to HVPG and liver function parameters. Furthermore, Pro-C5 was combined in a linear regression model.

Plasma Pro-C5 correlated to HVPG, indocyanine green clearance, sustained vascular resistance and mean arterial pressure (r = -0.68-0.33, p < 0.0001). A multiple regression analysis including Pro-C5, alanine aminotransferase, bilirubin and model for end-stage liver disease (MELD) improved the correlation to HVPG (r = 0.74, p < 0.0001). Plasma Pro-C5 was positively or negatively correlated to a number of routine liver function markers and MELD score (r = 0.27-0.68; p < 0.05-0.0001). Furthermore, plasma Pro-C5 could clearly separate patients with a HVPG <10 mmHg or HVPG ≥10 mmHg (p < 0.001, area under the curve (AUC) = 0.73), HVPG 10-<16 mmHg or HVPG ≥16 mmHg (p < 0.001, AUC = 0.68) and controls from diseased patients (p < 0.0001, AUC = 0.88). Finally, there was a clear relation to increasing Child score A-C and plasma Pro-C5 (ANOVA p < 0.001).

Plasma Pro-C5 reflects liver hemodynamics, liver function, disease stage and clinically significant portal hypertension (PH). A multimarker model in combination with clinical scores predicted HVPG and separated clinical relevant HVPG thresholds. Plasma Pro-C5 may be suitable for the noninvasive evaluation of PH in patients with cirrhosis.

Portal pressure is estimated through measuring the hepatic venous pressure gradient (HVPG). The main clinical applications of HVPG measurements include diagnosis, classification, and monitoring of portal hypertension, risk stratification, identification of candidates for liver resection, and monitoring efficacy of β-adrenergic blockers. Clinically significant portal hypertension is defined as an HVPG of 10 mm Hg or greater. Patients who experience a reduction in the HVPG of 20% or greater or to lower than 12 mm Hg in response to β-blocker therapy have a markedly decreased risk of bleeding (or rebleeding), ascites, and spontaneous bacterial peritonitis, resulting in improved survival rates.

Pain management in patients with liver cirrhosis is a real challenge and is often inadequate due to a lack of therapeutic efficacy or the high incidence of adverse effects. The focus of treatment differs depending on whether the pain is acute or chronic and involves understanding the causative pathophysiological mechanism. Analgesics should be started with the minimum effective dose and should be titrated slowly with avoidance of polypharmacy. Adverse effects must be monitored, especially sedation and constipation, which predispose the patient to the development of hepatic encephalopathy. The first-line drug is paracetamol, which is safe at doses of 2-3g/day. Non-steroidal anti-inflammatory agents are contraindicated because they can cause acute renal failure and/or gastrointestinal bleeding. Tramadol is a safe option for moderate-severe pain. The opioids with the best safety profile are fentanyl and hydromorphone, with methadone as an alternative. Topical treatment can reduce oral drug consumption. In neuropathic pain the first-line therapeutic option is gabapentin. The use of antidepressants such as amitriptyline can be considered in some patients. Interventional techniques are a valuable tool in moderate to severe pain, since they allow a reduction in drug therapy and consequently its adverse effects. Psychological treatment, physical therapy and rehabilitation should be considered as part of multimodality therapy in the management of chronic pain.

Non-invasive methods for assessment of hepatic fibrosis are increasingly needed. Recent studies showed that combined elevation of tumor markers CA 19-9 and CA 125 is predictive of severe hepatic fibrosis or cirrhosis with high specificity.

We aimed at developing a new panel of surrogate biomarkers for prediction of the stage of hepatic fibrosis by combining tumor markers with other known biomarkers of hepatic fibrosis.

A total of 92 patients with different types of chronic liver diseases (chronic hepatitis B, chronic hepatitis C and autoimmune hepatitis), were prospectively enrolled in our cohort. They were subjected to: ALT, AST, GGT, ALP, total bilirubin, INR, total cholesterol, albumin, platelet count, cancer antigen 19-9 (CA 19-9), cancer antigen 125 (CA 125), cancer antigen 15-3 (CA 15-3), haptoglobin, alpha-2-macroglobulin, apolipoprotein A1, abdominal ultrasound, liver biopsy and histological staging of hepatic fibrosis using the METAVIR system.

Combined elevation of CA 19-9 and CA 125 with a summated value > 37 U/mL is predictive of severe hepatic fibrosis or cirrhosis (stage F3-F4 METAVIR) with a probability of 77.6%. Multivariate analysis showed that the most relevant collection of biomarkers for prediction of stage of hepatic fibrosis is: CA 19-9, age, alpha-2- macroglobulin, total bilirubin, platelet count & albumin. We developed a new score, named the "Egy-Score", using a regression equation composed of this panel of biomarkers. Egy-Score could differentiate no or early fibrosis (stage F0-F2 METAVIR) from severe fibrosis or cirrhosis (stage F3-F4 METAVIR) with 83.7% accuracy.

Non-invasive assessment of hepatic fibrosis could be done using the Egy-Score. Egy-Score could differentiate no or early fibrosis (stage F0-F2 METAVIR) from severe fibrosis or cirrhosis (stage F3 - F4 METAVIR) with 83.7% accuracy.

Obesity is sharply rising worldwide and is increasingly recognized in patients with cirrhosis. This review summarizes the available data documenting a detrimental role of obesity and insulin-resistance on the risk of appearance of clinical events in patients with cirrhosis. Molecular pathways explaining the harmful effect of obesity and insulin resistance in the natural history of cirrhosis are largely unknown. Increasing knowledge of mechanisms leading to white adipose tissue dysfunction on one side, and to portal hypertension on the other side, allow hypothesizing that a link between the pathophysiology of obesity, insulin resistance and portal hypertension in cirrhosis exists. Mechanisms likely involved in this interplay are discussed in this article.

Accurate determination of the presence and degree of fibrosis in liver is of great importance, because the prognosis and management strategies for chronic liver disease depend mainly on these factors. To date, liver biopsy (LB) remains the "gold standard" for assessing the severity of liver fibrosis; however, LB is often limited by its invasiveness, sampling error, and intra/inter-observer variability in histological interpretation. Furthermore, repeated LB examinations within a short time interval are indeed ineligible in a real clinical practice. Thus, due to the pressing need for non-invasive surrogates for liver fibrosis, transient elastography (TE), as a novel ultrasound based technology, has allowed a noninvasive measurement of liver stiffness and has gained in popularity over recent years. In the past few years, additional roles for transient TE beyond the initial purpose of a non-invasive surrogate for LB have included the prediction of the most two critical consequences of fibrosis progression: the development of portal hypertension-related complications and hepatocellular carcinoma. This indicates that the role of transient TE is not merely limited to reducing the need for LB, but transient TE can enable the establishment of tailored management strategies by providing more detailed prognostic information. In particular, under the concept in which the clinical course of liver fibrosis is dynamic and bidirectional, especially when appropriate intervention is commenced, transient TE can be used to track the dynamic changes in fibrotic burden during antiviral or antifibrotic treatment. This review discussed extended applications of transient TE in prediction of the development of real clinical endpoints from a longitudinal perspective.