Different Stages Of Liver Cirrhosis Research Articles

Liver resection versus microwave ablation for solitary and small (≤ 3 cm) HCC with early recurrence in different stages of liver cirrhosis: A propensity score matching study

BackgroundThis study aimed to compare the effectiveness of liver resection (LR) and microwave ablation (MWA) in hepatocellular carcinoma (HCC) patients with early recurrence and varying stages of cirrhosis. MethodThis study analyzed patients with HCC who underwent hepatectomy and experienced early tumor recurrence (≤3 cm) between December 2002 and December 2020 at the Tongji Hospital. Treatment effectiveness was assessed using a propensity score matching (PSM) analysis. ResultsThis study included 295 patients (106, LR; 189, MWA), 86 patients in each of the 2 groups were chosen for further comparison, after PSM. After PSM, both LR and MWA demonstrated similar recurrence-free survival (RFS) and overall survival (OS) rates (p = 0.060 and p = 0.118, respectively). However, the LR group had more treatment-related complications. In patients with moderate or severe cirrhosis, no significant differences in RFS or OS rates were found between the LR and MWA groups (p = 0.779 and p = 0.772, respectively). In patients without cirrhosis or with mild cirrhosis, LR showed better RFS and OS rates than MWA (p = 0.024 and p = 0.047, respectively). Multivariate analysis after PSM identified moderate or severe cirrhosis and recurrence intervals ≤12 months as independent predictors of poor RFS and OS in patients with early recurrence of HCC. ConclusionLR is more effective than MWA for early recurrence of HCC in patients without cirrhosis or with mild cirrhosis, showing improved RFS and OS rates. In patients with moderate or severe cirrhosis, the OS and RFS were statistically equal between the two therapies. However, MWA may be preferred owing to its low complication rate.

The Comparison of Serum Interleukin-8 Levels Based on Severity of Liver Cirrhosis.

The molecule known as Interleukin-8 (IL-8), a chemotactic leukocyte, has been found to have a crucial role in the perpetuation of the inflammatory environment that is associated with hepatitis B virus (HBV) infection, as well as in the development of liver cirrhosis and cancer. The aim of this study was to carefully examine the role of IL-8 in the inflammatory reaction and to compare the levels based on the severity of liver cirrhosis. The study was conducted from February 2018 to September 2018 at the Gastroenterohepatology Division, Internal medicine Department, Faculty of Medicine, Universitas Sumatera Utara. The study was designed as an analytic comparative, cross-sectional study. The liver cirrhosis patients who participated in this study met the inclusion criteria and provided informed consent. A total of 70 patients were included in the study, from which we identified 1 individual with child-pugh A, 28 individuals with child-pugh B, and 41 individuals with child-pugh C. The serum level of IL-8 was found to be 98 (11-320) (pg/ml). The IL-8 levels between child-pugh B and C patients did not exhibit any noteworthy differences during our analysis (p = 0.109, p>0.05). There is no notable inequality in the levels of IL-8 across different stages of liver cirrhosis.

Antimitochondrial antibody associated with liver cirrhosis in patients with primary biliary cholangitis.

Antimitochondrial antibody (AMA) serves as a serological marker for diagnosing primary biliary cholangitis (PBC). However, the association between AMA and prognosis for PBC patients remains unclear. The objective of this study was to investigate the relationship between AMA and cirrhosis in PBC patients. This retrospective study enrolled 225 PBC patients, including 127 with liver cirrhosis and 98 without cirrhosis. AMA was tested by indirect immunofluorescence (IIF) with rat kidney as the substrate. AMA-M2 and M2-3E were detected by line immunoassay (LIA). The overall positivity rate for AMA detection in PBC patients was 80.9%. The positivity rates of IIF-AMA, AMA-M2, and M2-3E were significantly higher in patients with liver cirrhosis than in those without cirrhosis (73.2% vs. 52.0%, 74.0% vs. 51.0%, and 80.3% vs. 60.2%, respectively). In multivariate logistic regression, IIF-AMA (OR: 3.05, 95% CI: 1.59-5.87), AMA-M2 (OR: 3.11, 95% CI: 1.61-6.01), and M2-3E (OR: 3.29, 95% CI: 1.63-6.66) remained significantly associated with an increased incidence of liver cirrhosis. Moreover, in multinomial logistic regression, IIF-AMA (compensated cirrhosis, OR: 3.55, 95% CI: 1.49-8.44; decompensated cirrhosis, OR: 2.86, 95% CI: 1.32-6.18), AMA-M2 (compensated cirrhosis, OR: 4.74, 95% CI: 1.94-11.58; decompensated cirrhosis, OR: 2.51, 95% CI: 1.19-5.33), and M2-3E (compensated cirrhosis, OR: 4.92, 95% CI: 1.74-13.96; decompensated cirrhosis, OR: 2.91, 95% CI: 1.28-6.64) were all found to be associated with different stages of liver cirrhosis. AMA was found to be associated with the occurrence of liver cirrhosis in PBC patients. Additionally, AMA was also related to different stages of liver cirrhosis, including compensated and decompensated cirrhosis.

Current pathophysiological concepts of acute decompensation in patients with liver cirrhosis and prognostic scores in different stages of disease

Acute decompensation and acute-on chronic liver failure (ACLF) are associated with a significant reduced prognosis. Previously, the pathophysiological concept of acute decompensation was mainly based on the peripheral vasodilatation hypothesis. However, during the last years, systemic inflammation was recognized as a major driver for decompensation of liver cirrhosis and ACLF. Further, it has been shown that systemic inflammation is associated with the clinical course and the prognosis of the patients. Inflammation also affects the function of extrahepatic organs and therefore leads to the development of an inflammatory cirrhotic multi-organ syndrome. The importance of systemic inflammation in the context of decompensated liver cirrhosis is also transferred to new clinical scores such as the CLIF-C AD and CLIF-C ACLF score. In this article, we provide an overview of the new systemic inflammation hypothesis of decompensated cirrhosis and also discuss current clinical scores for prognostication in different stages of liver cirrhosis.

A novel index for staging hepatitis B related liver cirrhosis in patients with hepatocellular carcinoma.

Information on the stage of liver cirrhosis is essential for prognostication and decisions on surgical planning for hepatocellular carcinoma (HCC) patients. But a non-invasive liver cirrhosis staging model is still lacking. The aim of our study was to develop a non-invasive model based on routine clinical parameters to evaluate the severity of cirrhosis in hepatitis B related HCC patients. A total of 226 HCC patients with chronic hepatitis B virus (HBV) infection who had liver resection were analyzed in this retrospective study. We found that platelets, prothrombin activity, maximum oblique diameter of right hepatic lobe and spleen length were the independent predictors of liver cirrhosis in HCC patients. By cumulating the weight of risk scores of independent variables, we constructed the PPMS (PLT/PTA/maximum oblique diameter of right hepatic lob/spleen length) index. The areas under the receiver operating characteristic curves (AUROC) of PPMS index were 0.820, 0.667, and 0.650 in predicting ≥cirrhosis 1 (C1), ≥cirrhosis 2 (C2), and ≥cirrhosis 3 (C3), respectively. The optimal cut-off value of the PPMS index for predicting ≥C1, ≥C2, and ≥C3 was 4.392, 4.471, and 4.784, respectively. And the corresponding sensitivity was 63.1%, 63.2%, and 64.7%, the corresponding specificity was 89.4%, 64.3%, and 62.5%, respectively. Our study constructed a non-invasive liver cirrhosis index (PPMS) could distinguish patients from different stages of liver cirrhosis, which might add more preoperative information for HCC patients.

Development and Evaluation of a Physiologically Based Pharmacokinetic Drug-Disease Model of Propranolol for Suggesting Model Informed Dosing in Liver Cirrhosis Patients.

AimThe study was aimed to understand the underlying causes for the differences in propranolol pharmacokinetics (PK) between healthy and cirrhosis populations by using a systematic whole-body physiologically based pharmacokinetic (PBPK) model-building approach for suggesting model informed propranolol dosing in liver cirrhosis patients with different stages of disease severity.MethodsA whole-body PBPK model was developed by using population simulator PK-Sim® by using reported physicochemical and clinical data for propranolol in healthy and liver cirrhosis populations. The model evaluation was done by visual verification and comparison of PK parameters using their observed/predicted ratios (Robs/pred).ResultsThe developed model has effectively described the disposition of propranolol after intravenous and oral application in healthy and liver cirrhosis populations. All the model predictions were comparable to the observed clinical data and the Robs/pred for all the PK parameters were within a 2-fold range. A significant increase in plasma concentration of propranolol and decrease in drug clearance was observed in progressive stages of liver cirrhosis. The developed model after evaluation with the reported clinical PK data was used for suggesting model informed propranolol dosing in different stages of liver cirrhosis based on systemic unbound drug concentration.ConclusionThe developed PBPK model has successfully described propranolol PK in healthy and cirrhosis populations after IV and oral administration. The evaluated PBPK propranolol-cirrhosis model can have many implications in predicting propranolol dosing in liver cirrhosis patients with different stages of disease severity.

Translation of IRF-1 Restricts Hepatic Interleukin-7 Production to Types I and II Interferons: Implications for Hepatic Immunity.

Interleukin-7 (IL-7) is an important cytokine with pivotal pro-survival functions in the adaptive immune system. However, the role of IL-7 in innate immunity is not fully understood. In the present study, the impact of hepatic IL-7 on innate immune cells was assessed by functional experiments as well as in patients with different stages of liver cirrhosis or acute-on-chronic liver failure (ACLF). Human hepatocytes and liver sinusoidal endothelial cells secreted IL-7 in response to stimulation with interferons (IFNs) of type I and II, yet not type III. De novo translation of interferon-response factor-1 (IRF-1) restricted IL-7 production to stimulation with type I and II IFNs. LPS-primed human macrophages were identified as innate immune target cells responding to IL-7 signaling by inactivation of Glycogen synthase kinase-3 (GSK3). IL-7-mediated GSK3 inactivation augmented LPS-induced secretion of pro-inflammatory cytokines and blunted LPS tolerance of macrophages. The IFN-IRF-1-IL-7 axis was present in liver cirrhosis patients. However, liver cirrhosis patients with or without ACLF had significantly lower concentrations of IL-7 in serum compared to healthy controls, which might contribute to LPS-tolerance in these patients. In conclusion, we propose the presence of an inflammatory cascade where IFNs of type I/II induce hepatocellular IL-7 in an IRF-1-restriced way. Beyond its role in adaptive immune responses, IL-7 appears to augment the response of macrophages to LPS and to ameliorate LPS tolerance, which may improve innate immune responses against invading pathogens.

Comparatyive determination of proteins, nitrogen-containing compounds and lipids content in blood plasma and ascitic fluid in patients with liver cirrhosis

The aim of the work is the determination of proteins concentration in blood plasma and ascetic fluid and also toxic and atherogenic properties of ascitic fluid in patients with different stages of liver cirrhosis for the further choice of the individual treating tactics.Research methods: 262 patients with liver cirrhosis, according to the diagnostic examination, who demonstrated the different severity of the pathological process in the liver parenchyma, were divided in 4 groups. In blood plasma and ascitic fluid of patients with liver cirrhosis were determined the concentration of protein, general content of bilirubin, concentration of final nitrogen, creatinine, urea, cholesterol and lecithin. Results: the obtained results demonstrate the disorder of the protein homeostasis and increase of the content of atherogenic lipoproteins, as a result of which hepatocyte membrane structures in patients with liver cirrhosis are destructed. The content of studied components in ascitic fluid was identical (and sometimes even more) to the one in blood plasma – it allows to consider ascitic fluid as a plasma-replacing component in patients with liver cirrhosis, especially at the hepatic failure progression.The degree of the disorder of the functional activity of the liver parenchyma was studied. The author of the article concludes that at choosing the surgical tactics in patients with liver cirrhosis, complicated with acsites, the degree of homeostasis disorders expressiveness must be taken into account

Liver cirrhosis stages and the incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving antiviral therapy

Objectives: Long-term antiviral therapy decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB), however, it cannot eliminate the risk. We investigated the incidence of HCC at different stages of liver cirrhosis (LC) and identified clinical predictors for HCC development during antiviral therapy.Methods: The data from 356 treatment-naïve patients aged 40 to 69 years without a history of HCC who had received entecavir for ≥6 months were collected retrospectively. The incidence of HCC was evaluated in patients with CHB only, with LC without varices (stage 1), with varices (stage 2), and with ascites (stage 3).Results: The median follow-up period was 3.6 years. In total, 45 patients (12.6%) developed HCC. The annual incidence rates of HCC in patients with CHB only or LC in stages 1, 2, and 3 were 0.4%, 2.6%, 9.8%, and 6.7%, respectively. In multivariate analyzes, LC at stage 2 (hazard ratio [HR] 17.16, 95% confidence interval [C.I.] 3.93–75.01, p < .001), alcohol consumption (HR 3.84, 95% C.I. 1.99–7.39, p < .001), and older age (HR 1.06, 95% C.I. 1.01–1.11, p = .010) were significantly associated with HCC development. The risk decreased in those who stopped drinking after 2 years of abstinence (p = .0314).Conclusions: LC with significant portal hypertension (varices or ascites), alcohol consumption, and older age at the time of starting antiviral therapy are independent predictors for future HCC development.

Biomarkers and Liver Disease: Can We Predict Decompensation with suPAR?

Release of urokinase plasminogen activator receptor (uPAR, CD87), shedded from leukocytes into serum as soluble uPAR (suPAR) is a novel clinical biomarker for immune activation and prognosis in many acute and chronic inflammatory disorders like sepsis or chronic kidney disease. We herein review the current literature on suPAR in patients with liver diseases. Serum suPAR levels are upregulated and indicate disease severity in acute liver failure, chronic hepatitis, and different stages of liver cirrhosis. In prospective studies, high suPAR serum concentration predicted decompensation, organ failure, hepatocellular carcinoma (HCC), and mortality in patients with advanced chronic liver diseases. However, suPAR is not suitable as a diagnostic tool in liver diseases, as it reflects systemic inflammation and organ dysfunction in various acute or chronic illnesses. Measuring circulating suPAR can provide substantial additional prognostic information and should therefore be considered as an interesting biomarker in liver disease patients.

Limited comparability of creatinine assays in patients with liver cirrhosis and their impact on the MELD score

Background & aimPatients with end-stage liver disease require valid estimations of mortality for organ allocation and risk stratification. The model of end-stage liver disease (MELD) score is used for this purpose in most countries and incorporates bilirubin, International Normalized ratio, and creatinine. The aim of this study was to evaluate the comparability of creatinine results from different routine assays in the serum samples of patients with liver cirrhosis. MethodsResidual material from 60 serum samples was available from patients in different stages of liver cirrhosis. Four centers participated; each center analyzed the samples with Jaffé-based and enzymatic routine assays in parallel. In addition, an accredited calibration laboratory certified the panel of samples by an internationally accepted reference measurement procedure (RMP) based on isotope dilution mass spectrometry (ID-MS). This method served as the independent reference. ResultsAll routine methods displayed a high correlation to the RMP (r ≥0.937, p<0.001). Two enzymatic and two Jaffé-based methods provided results that were all within a ±20% range of the RMP. The other methods showed deviations >20% in up to 27% of the samples. The enzymatic methods were systematically lower, whereas the Jaffé-based methods were systematically higher (p<0.001). The resulting MELD scores differed from 0 to 4 points. ConclusionsThere are systematic deviations from the RMP. Jaffé-based assays gave higher results, whereas the enzymatic-based assays gave lower results compared to the results of the RMP. The comparability of results is limited and could be disadvantageous to patients listed for liver transplantation.

Morphology and molecular study of Fascioloides magna – a growing threat to cervids (Cervidae) in Poland

Abstract Introduction: The giant liver fluke, Fascioloides magna, has spread across Europe over the years posing a serious threat to the Polish cervid population. Material and Methods: Macroscopic and histopathological studies of the liver of 22 roe deer (Capreolus capreolus), 10 red deer (Cervus elaphus), and 6 fallow deer (Dama dama) were performed. Species determination of the recovered liver flukes and eggs was performed by PCR protocol amplifying fragments of ribosomal DNA (ITS2), according to a standard method. Results: The presence of F. magna was confirmed in three (13.6%) roe deer, seven (70.0%) red deer, and two (33.3%) fallow deer. The fluke eggs were found only in the stools of five red deer and one fallow deer. Conclusion: This study presents detailed pathological and histopathological changes in the liver of wild Polish cervids, including roe deer, which were subjected to such study for the first time. The hepatic lesions typical for different stages of liver cirrhosis varied depending on the host species and stage of the disease.

Inhibiting miR-21 attenuates experimental hepatic fibrosis by suppressing both the ERK1 pathway in HSC and hepatocyte EMT.

MicroRNA-21 (miR-21) has emerged as a critical regulatory molecule and an important serum marker in hepatic fibrogenesis. The aim of the present study was to investigate the role of inhibiting miR-21 on hepatic fibrosis treatment. Serum miR-21 levels in 60 healthy individuals and 180 patients with different stages of liver cirrhosis were examined, miR-21 levels in normal or cirrhotic human liver tissues (n=10 each) were also detected. An adenoviral vector (Ad-TuD-21) carrying the sponging ToughDecoy (TuD)-RNA sequence against miR-21 was constructed to reduce miR-21 expression efficiently invitro and invivo Histological and immunohistological examinations were performed to evaluate the inhibitory effects and mechanism of Ad-TuD-21 delivery into carbon tetrachloride (CCl4) induced hepatic fibrosis rats by targeting extracellular signal-regulated kinase 1 (ERK1) signalling in hepatic stellate cells (HSC) and hepatocyte epithelial-mesenchymal transition (EMT). Our results revealed that enhanced miR-21 levels in cirrhotic patients were related to the severity and activity of liver cirrhosis. Ad-TuD-21 administered to liver fibrosis rats could remarkably suppress profibrotic gene expression, cause histological improvements in liver and attenuate hepatic fibrosis significantly. More importantly, after Ad-TuD-21 treatment, inhibition of both the ERK1 signalling pathway in HSC and hepatocyte EMT was confirmed, which paralleled the enhancement of miR-21 target genes-sprouty2 (SPRY2) and hepatocyte nuclear factor 4α (HNF4α)-expression invivo These data demonstrated that miR-21 is a key regulator to promote hepatic fibrogenesis, and sponging miR-21 expression may present a novel potentially therapeutic option for hepatic fibrosis.

Serum Bile Acids Are Associated with Pathological Progression of Hepatitis B-Induced Cirrhosis.

Recent metabonomic studies have identified an important role of bile acids in patients with liver cirrhosis. Serum bile acids, such as glycocholate (GCA), glycochenodeoxycholate (GCDCA), taurocholate (TCA), and taurochenodeoxycholate (TCDCA), increased significantly in liver cirrhosis patients. Our recently published urinary metabonomic study showed that glycocholate 3-glucuronide, taurohyocholate, TCA, glycolithocholate 3-sulfate, and glycoursodeoxycholate (GUDCA) were markedly increased in hepatitis B-induced cirrhotic patients (n = 63) compared with healthy controls (n = 31). The urinary levels of GUDCA were able to differentiate among three stages of cirrhotic patients with Child-Pugh (CP) score A, B, and C. In this study, we recruited two new cohorts of patients with hepatitis-B-induced cirrhosis and healthy control subjects and quantitatively profiled their serum bile acids using ultra-performance liquid chromatography triple quadrupole mass spectrometry. Serum bile acid profile and corresponding differential bile acids were characterized, in addition to the blood routine, liver, and renal function tests. The alterations of bile acids contributing to the intergroup variation between healthy controls and cirrhotic patients and among pathological stages of CP grade A, B and C were also investigated. Five bile acids, GCA, GCDCA, TCA, TCDCA, and GUDCA, were significantly altered among different stages of liver cirrhosis (n = 85), which was validated with an independent cohort of cirrhotic patients (n = 53). Our results show that dynamic alteration of serum bile acids is indicative of an exacerbated liver function, highlighting their potential as biomarkers for staging the liver cirrhosis and monitoring its progression.

Effect of Alcohol Consumption and Oxidative Stress and Its Role in DNA Damage

Oxidative stress has been increasingly implicated in different stages of liver cirrhosis and has been found responsible for DNA damage. Alcohol consumption and oxidative stress have been linked with DNA damage and progression of disease, leading to the hypothesis that chronic alcoholism causes DNA damage. The study was aimed at evaluating the relation between alcohol consumption and relative oxidative damage in different stages of liver cirrhosis. The study included two groups based on severity of cirrhosis of liver; categorized as compensated and decompensated liver cirrhotic patients based on child Pugh criteria. All decompensated cirrhotic patients in the study group had significantly higher MDA levels (P 0.01) than those with compensated cirrhotic patients and control group who were not suffering from liver cirrhosis. These results highlighted a significant higher degree of DNA damage in decompensated cirrhotic patients associated with oxidative stress as shown from greater average DNA migration in decompensated cirrhotic patients than in the compensated cirrhotic patients with low level of oxidative stress. Thus these results suggest that increase in MDA levels may be associated with pathogenesis and progression of liver cirrhosis.

Role of cystatin C and renal resistive index in assessment of renal function in patients with liver cirrhosis

To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis. We conducted a study of 63 patients with liver cirrhosis. A control group comprised of 30 age and gender-matched healthy persons. Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made. Estimated glomerular filtration rate from serum creatinine (GFRCr) and cystatin C (GFRCys) was calculated. We confirmed significant differences in values of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh (P = 0.01), and a significant correlation with model of end stage liver disease (MELD) score (r s = 0.527, P < 0.001). More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr (P < 0.001). Significantly higher renal resistive index was noted in Child-Pugh C than in A (P < 0.001) and B stage (P = 0.001). Also, a significant correlation between renal resistive index and MELD score was observed (r s = 0.607, P < 0.001). Renal resistive index correlated significantly with cystatin C (r s = 0.283, P = 0.028) and showed a negative correlation with GFRCys (r s = -0.31, P = 0.016). Cystatin C may be a more reliable marker for assessment of liver insufficiency. Additionally, cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis.

Diffusion-weighted imaging (DWI) of the spleen in patients with liver cirrhosis and portal hypertension

ObjectiveThe purpose of this study was to assess the influence of liver cirrhosis and portal hypertension on diffusion coefficients of the spleen. Material and MethodsWe retrospectively evaluated 50 patients with liver cirrhosis and 50 patients without any history of liver disease who underwent magnetic resonance imaging of the upper abdomen, including echo planar diffusion-weighted imaging using b values of 50, 300 and 600mm2/s. Spleen apparent diffusion coefficient (ADC), liver ADC, muscle ADC and normalized spleen ADC (defined as the ratio of spleen ADC to muscle ADC) were compared between cirrhotic patients and patients in the control group and correlated with Child–Pugh stages. Reproducibility was assessed by measuring interclass correlation coefficient (n=11). Additionally, in eight patients, ADC measurements were performed 1 day before and 3 days after transjugular intrahepatic portosystemic shunt (TIPSS) implantation. ResultsCompared with control subjects, patients with cirrhosis and portal hypertension had significantly higher spleen ADCs (P=.0001). There was a statistically significant correlation between Child–Pugh grade and spleen ADC (Pearson correlation coefficient, observer 1 r=0.6, P=.0001; observer 2 r=0.5, P=.0001). After TIPSS implantation, we observed a reduction in spleen ADC values. Spleen ADC measurements showed a high reproducibility (interclass correlation coefficient 0.75, P=.001). ConclusionOur data suggest that different stages of liver cirrhosis and portal hypertension correlate with ADC values of the spleen. Furthermore, ADC values of the spleen decrease after TIPSS implantation. Further studies are required to understand the potential clinical values of these observations.

Ultrasonographic Prevalence and Factors Predicting Left Ventricular Diastolic Dysfunction in Patients with Liver Cirrhosis: Is There a Correlation between the Grade of Diastolic Dysfunction and the Grade of Liver Disease?

Presence of cardiac dysfunction has been associated with an unfavorable prognosis in patients with liver cirrhosis. In the present study, 92 consecutive, newly-diagnosed patients with liver cirrhosis were prospectively evaluated. Liver disease was graded according to the modified Child-Turcotte-Pugh (CTP) score whereas left ventricular diastolic function was assessed by Doppler-echocardiography and graded (Stage 0 to 4) according to current guidelines. Overall, DD was diagnosed in 55/92 (59.8%) patients [DD-stage-1: 36/92 (39.1%), DD-stage-2: 19/92 (20.6%)]. Prevalence of DD-stage-1 among the different stages of liver cirrhosis was: CTP-class A: 11/29 (37.9%), B: 15/39 (38.5%), C: 10/24 (41.6%), (P > 0.05 in all comparisons), whereas for DD-stage-2 the corresponding proportions were CTP-class A: 3/29 (10.3%), B: 5/39 (12.8%), C: 11/24 (45.8%), (P = 0.0009 between CTP-class C versus A and B). Age > 53 years (Odd's Ratio [OR]: 4.2; 95% confidence interval [CI]: 1.5–12.1) and CTP-class C (OR: 4.6; 95% CI: 1.1–20) could independently predict DD. No relation between presence of DD and the etiology of the liver disease was found. We conclude that DD is a common feature in liver cirrhosis. DD-stage-1 is fairly prevalent among all CTP-classes whereas DD-stage-2 seems to be characteristic of the advanced liver disease (CTP-class C). A high level of awareness for the presence of the syndrome is required, especially if cirrhotic patients are CTP-class C and/or of older age.

Renal Effects of the Novel Selective Adenosine A1 Receptor Blocker SLV329 in Experimental Liver Cirrhosis in Rats

Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A1 receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A1 receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (−36.5%, p<0.05), especially in those receiving furosemide (−41.9%, p<0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A1 receptor antagonists are clinically beneficial at different stages of liver cirrhosis.

Sorafenib Therapy in Patients with Advanced Hepatocellular Carcinoma in Advanced Liver Cirrhosis

Background and Aim: Sorafenib has become the treatment standard for patients with advanced hepatocellular carcinoma (HCC). It is not clear whether patients with advanced liver function impairment (Child B) and patients undergoing additional locoregional therapy may tolerate treatment with sorafenib and benefit. We aimed to evaluate the tolerability and efficiency of sorafenib in patients with advanced HCC and different stages of liver cirrhosis, and in combination with locoregional therapy. Methods: In 50 patients with advanced HCC treated with sorafenib tolerability and efficiency of the therapy with respect to stage of liver cirrhosis, existence of extrahepatic tumor spread, and additional locoregional therapy were evaluated. Results: Fifty patients with advanced HCC were treated with sorafenib, and 13 received additional locoregional therapy. Tolerability of the systemic treatment was moderate in all patients, with no significant differences between the subgroups, while the median survival was better in patients with Child A than Child B cirrhosis. Conclusion: Tolerability and toxicity of a systemic treatment with sorafenib are moderate in patients with liver cirrhosis in Child A or B. Prospective randomized studies are required to evaluate the efficacy and tolerability of combined systemic and locoregional treatment approaches in patients with advanced HCC.