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Liver stiffness (LS) is a novel non-invasive parameter widely used in clinical hepatology. LS correlates with liver fibrosis stage in non-cirrhotic patients. In cirrhotic patients it also shows good correlation with Hepatic Venous Pressure Gradient (HVPG). Our aim was to assess the contribution of liver fibrosis and portal hypertension to LS in patients with advanced liver cirrhosis. Eighty-one liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG and LS measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France). Liver collagen content was assessed in the explanted liver as collagen proportionate area (CPA) and hydroxyproline content (HP). The studied cohort included predominantly patients with Child-Pugh class B and C (63/81, 77.8 %), minority of patients were Child-Pugh A (18/81, 22.2 %). LS showed the best correlation with HVPG (r=0.719, p

OBJECTIVE Respiratory alkalosis (RA) and dilutional hyperchloremic acidosis (DHA) are the most common acid-base balance (ABB) disorders in patients with liver cirrhosis. The aims of this study were to clarify whether RA develops in relation to DHA via respiratory compensation of metabolic acidosis and whether spironolactone in combination with low-dose furosemide - diuretics known to ameliorate DHA - positively affects RA in liver cirrhosis patients. MATERIALS AND METHODS 59 patients with advanced cirrhosis were divided into two groups. Group D consisted of individuals (urine sodium concentration (UNa+) > 20 mmol/L) who responded to combination therapy consisting of spironolactone and low-dose furosemide. The non-D group consisted of individuals (UNa+ ≤ 20 mmol/L) who either did not respond to the treatment or who were not administered it. In both groups, we examined serum and urine concentrations of electrolytes and ABB parameters, including SNa+-SCl- and SNa+/SCl- values. RESULTS In group D, we found a statistically significant relationship between pCO2 and SHCO3-: r = 0.756 (p < 0.001) and between pCO2 and SNa+-SCl-: r = 0.522 (p = 0.001). Neither Salb nor the corrected anion gap were associated with changes in SHCO3- or pCO2 values. Although SHCO3- values were normal, abnormal pCO2 values were observed in one third of group D patients. Based on multivariable analysis, SHCO3- proved to be a statistically significant influencing factor on pCO2 values. CONCLUSION DHA contributes to the development of RA in individuals with liver cirrhosis. Reducing DHA by means of effective diuretic therapy comprising spironolactone and furosemide has a beneficial effect on RA in such patients.

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.

Liver stiffness is a reliable non-invasive predictor of Hepatic Venous Pressure Gradient (HVPG) above 10 mm Hg. However, it failed to predict higher thresholds of HVPG. Our aim was to investigate whether liver stiffness and selected previously published non-invasive blood biomarkers could predict higher HVPG thresholds in liver transplant candidates without ongoing alcohol use. One hundred and nine liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG measurement, liver stiffness measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France) and assessment of blood HVPG biomarkers (osteopontin, VCAM-1, IL-6, TNF-α, IL-1ra/IL-1F3 and ELF score). The correlation between liver stiffness and HVPG was linear up to 30 mm Hg of HVPG (r = 0.765, p < 0.0001). The regression lines had similar slopes for HVPG values below and above 16 mm Hg (p > 0.05) and the correlation in patients with HVPG

In patients with advanced cirrhosis with ascites disorders of water and electrolyte metabolism are often present and they are associated with changes in acid-base balance. These changes can be very complicated, their diagnosis and treatment difficult. Dilutional hyponatremia is the most common disorder. Hyponatremia in these patients is associated with increased morbidity and mortality before and after liver transplantation. Other common disorders include hyperchloremic acidosis, hypokalemia, metabolic alkalosis, lactic acidosis, respiratory alkalosis. If renal impairment occurs (for example hepatorenal syndrome), metabolic acidosis and retention of acid metabolites may develop. The pathogenesis of these conditions applies primarily hemodynamic changes. Activation of renin-angiotensin-aldosterone system and non-osmotic stimulation of antidiuretic hormone trigger serious changes in water and natrium-chloride metabolism. This activation is clinically expressed like oedema, ascites, hydrothorax, low to zero natrium concentration in urine and increased urinary osmolality, which is higher than serum osmolality. In practice, the evaluation can be significantly modified by the ongoing diuretic therapy. Closer monitoring of water and electrolyte metabolism together with acid-base balance in patients with ascitic liver cirrhosis is important, not only in terms of diagnosis but especially in terms of therapy.

Adenomas of the liver and focal nodular hyperplasia (FNH) are benign hepatocellular affection and their distinguishing in a needle biopsy sample and sometimes also in a surgical specimen causes often a problem. Although it might seem that the differentiation of the benign conditions is of a low value for the clinicians and also for the patients, the opposite is true. The risk of life-threatening bleeding and risk of the malignant transformation of adenomas leads to request accurate diagnosis of these conditions. New genetic methods followed by immunohistochemical detection of several antigens enables more accurate distinction not only of the two main groups of FNH and adenomas, but allows also to distinguish subsets of adenomas with varying risk of malignant transformation. Therefore, to determine the subtype of adenoma represents now essential part of a biopsy diagnosis. Identification of the subsets of adenomas allows an individualized treatment with resection in high-risk forms and, on the other hand, allows avoiding liver resection in the case of small liver mass with a low risk of malignant transformation.

Between April 1995 and November 2005, 500 liver transplantations were performed in 476 patients of age from 3, till 70, at the Transplantation center of the Institute of Clinical and Experimental Medicine (IKEM) in Prague. The most common indications for liver transplantation were alcoholic liver cirrhosis (23%), hepatitis C cirrhosis (17%), and cholestatic cirrhosis (PBC and PSC, 9% each). Mean MELD score of recipients at the transplantation was 15-18 for each year of transplantation. Ten-years patient survival was 79.1 +/- 2.2%, and graft survival 74.1 +/- 2.1% respectively. Best patient and graft survival was achieved among patients transplanted for autoimmune liver diseases, the worst in group of patients with alcoholic cirrhosis. Malignancies were the most common cause of death during the period of follow-up (17 patients).Patients were followed longitudinally at the Department of hepatogastroenterology IKEM according to prospective protocol included protocol biopsies. Hypertension (in 71% of recipients), and overweight or obesity (in 56.3%), were the most prevalent medical complications among long-term survivors. Diabetes was found in 28.6%, of which 14.7% was de-nove diabetes after transplantation. Renal insufficiency (S-creatinin150 micromol/l) was present in 61 of 348 (17.6%) survivors. Out of these, 16 needed chronic hemodialysis, and 12 underwent kidney transplantation subsequently. Protocol biopsy at 5 years after transplantation was evaluated in a sample of 102 unselected liver transplant recipients. Normal liver was found in 4% of recipients, minor non-specific changes in 36% of them. Disease recurrence was present in all of 16 recipients transplanted for HCV cirrhosis, in one third of them graft cirrhosis was already present. Disease recurrence was found in patients transplanted for autoimmune disease frequently, PBC in 40%, PSC in 25%, and autoimmune hepatitis in 60% of recipients. Graft steatosis greater than 33% was present in 13% of recipients.Liver transplantation is highly effective method of treatment of end stage liver disease. Despite frequent medical complications, and disease recurrence on histological examination almost 80% of recipients transplanted in the liver transplantation program in IKEM survived more than 10 years after procedure. The survival achieved was far above that of the European liver transplant registry.