Acute responses of hepatic fat content to consuming fat, glucose and fructose alone and in combination in non-obese non-diabetic individuals with non-alcoholic fatty liver disease.

We have recently demonstrated that a high-fat load can induce immediate increase in hepatic fat content (HFC) and that such an effect can be modified differently by co-administration of fructose or glucose in healthy subjects. Therefore, we addressed the question how consumption of these nutrients affects changes in HFC in subjects with non-alcoholic fatty liver disease (NAFLD). Eight male non-obese non-diabetic patients with NAFLD underwent 6 experiments each lasting 8 hours: 1. fasting, 2. high-fat load (150 g of fat (dairy cream) at time 0), 3. glucose (three doses of 50 g at 0, 2, and 4 hours), 4. high-fat load with three doses of 50 g of glucose, 5. fructose (three doses of 50 g at 0, 2, and 4 hours), 6. high-fat load with three doses of 50 g of fructose. HFC was measured using magnetic resonance spectroscopy prior to meal administration and 3 and 6 hours later. Plasma triglycerides, non-esterified fatty acids, glucose and insulin were monitored throughout each experiment. HFC increased by 10.4 ± 6.9% six hours after a high-fat load and by 15.2 ± 12.5% after high-fat load with fructose. When co-administering glucose with fat, HFC rose only transiently to return to baseline at 6 hours. Importantly, NAFLD subjects accumulated almost five times more fat in their livers than healthy subjects with normal HFC. Consumption of a high-fat load results in fat accumulation in the liver of NAFLD patients. Fat accumulation after a fat load is diminished by glucose but not fructose co-administration.

Portal hypertension is the main driver of liver stiffness in advanced liver cirrhosis.

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< 0.001), correlation of LS with CPA (r=0.441, p< 0.001) and HP/Amino Acids (r=0.414, p< 0.001) was weaker. Both variables expressing liver collagen content showed good correlation with each other (r=0.574, p<0.001). Multiple linear regression identified the strongest association between LS and HVPG (p < 0.0001) and weaker association of LS with CPA (p = 0.01883). Stepwise modelling showed minimal increase in r2 after addition of CPA to HVPG (0.5073 vs. 0.5513). The derived formula expressing LS value formation is: LS = 2.48 + (1.29 x HVPG) + (0.26 x CPA). We conclude that LS is determined predominantly by HVPG in patients with advanced liver cirrhosis whereas contribution of liver collagen content is relatively low.

Allograft hepatitis after liver transplantation for epithelioid haemangioendothelioma.

Primary hepatic epitheloid heamangioendothelioma (EHE) is a rare neoplasm of vascular origin. We present a retrospective study of 6 patients with EHE treated by liver transplantation that were monitored clinically for more than 3 years and had protocol biopsy samples taken at 1, 3, 5, 7, and 10 years posttransplant. None of the patients suffered from any form of viral or autoimmune hepatitis before or after the transplantation. Two patients had lung metastases detected by preoperative imaging. All tumours showed factor VIII, CD31, and CD34 strong positive staining. In 5 of the 6 transplant recipients the protocol graft biopsies showed chronic non-specific hepatitis with slowly progressive periportal fibrosis that appeared during the 3rd post-transplant year. The septal fibrosis was diagnosed in the 6th and 10th year after transplantation. Liver tests did not reflect either the presence or the degree of inflammation or fibrosis and have remained normal. In retrospect, we consider that our recipients most probably developed alloantigen dependent inflammatory and fibrotic damage to their liver grafts. All six recipients are still alive for a median survival time of 95.1 month (range 44 months to 132 months), with good graft function, and without recurrence of the tumor. The lung metastases in 2 of the 6 patients have remained unchanged for 10 and 12 years retrospectively.

[Long-term follow up of renal function after orthotopic liver transplantation]. / Dlouhodobé sledování funkce ledvin po ortotopické transplantaci jater.

BACKGROUND: Renal dysfunction in patients after the orthotopic liver transplantation (OLT) is frequent and it significantly contributes to the morbidity and mortality. The aim of our work was to assess the level of glomerular function (GFR) within the first to fifth year after OLT. METHODS AND RESULTS: Serum creatinine concentration (Skr), creatinine clearance (Ckr) and predicted value of creatinine clearance using the Cockcrofta a Gaulta formula (CG) were assessed in 75 patients. Normal values of the given parameters (Skr <110 umol/l, Ckr > or = 1.3 ml/s/1.73 m2) were found only in 16% of all patients. Significant decrease of GFR (Ckr < 0.5 ml/s/1.73 m2) was found in 24% of cases, acute renal failure, which required transitory haemodialysis developed in 4% of patients. In 60% of patients various degree of GFR decrease was found without the necessity of haemodialysis. CONCLUSIONS: Level of renal functions was not significantly related to the blood pressure or serum lipids concentration. An important factor appeared to be the level of renal function before OLT. Because the level of renal function after OLT can significantly influence the post transplantation development, regular follow up of GFR is recommended.

[Tubular function after orthotopic liver transplantation]. / Tubulární funkce u jedincu po ortotopické transplantaci jater.

Renal function after orthotopic liver transplantation (OTL) is very frequently reduced and its level exerts a significant effect on the morbidity and mortality of these subjects. One of the main factors with a negative impact on renal function after OTL is the nephrotoxic action of cyclosporin A (CsA). Renal function after OTL is usually evaluated on the basis of glomerular filtration (GF). As chronic nephrotoxicity of CsA is manifested in the histological picture by significant tubulointerstitial affection, in 75 subjects after OTL the spontaneous concentrating and acidifying capacity of the kidneys was investigated. The value of urine osmolality (UOSM) assessed after noctunal withdrawal of fluids was in 72.7% lower than in healthy subjects and did not reach 600 mOsm/kg H2O, although the serum creatinine concentration (Scr) was still within the normal range. The pH value of the morning urine did not reach in 38.2% the required value of 6.0 although Scr was within the normal range. Between values of UOSM after nocturnal liquid withdrawal and GF assessed on the basis of inulin clearance (Cin) was a significant direct relationship, however the scatter of values was considerable (r = 0.226, p < 0.05). Between pH values of the morning urine and Cin no correlation was found. The assembled results support the idea that the concentrating activity of the kidneys in subjects after OTL treated with CsA is reduced. This reduced concentrating capacity is already apparent on the basis of UOSM of morning urine after nocturnal fluid withdrawal. Although this defect is also frequent in subjects with a normal Scr value, the authors assume that the use of this simple evaluation of the concentrating capacity (it does not burden the patient nor the attending staff) could be useful in the early diagnosis of tubulointerstitial affection.