Heparin-like effect contributes to the coagulopathy in patients with acute liver failure undergoing liver transplantation.

INTRODUCTION: Liver transplantation (LT) in cirrhotics is characterized by severe coagulopathy, associated with a well documented heparin-like effect (HLE) seen by thromboelastography (TEG) after reperfusion. The amount of HLE present in patients with acute liver failure (ALF) and its role in their bleeding tendency before LT has not been investigated. AIM: To investigate the presence and extent of HLE in patients with ALF undergoing LT and to compare the extent of HLE in this group with a group of cirrhotics undergoing LT. MATERIAL AND METHODS: Ten consecutive ALF and 10 cirrhotic patients undergoing LT were included. TEG (with and without heparinase I), surrogate total thrombin generation (TTG) derived by TEG and haemodynamic variables were recorded for every stage of the LT. HLE was defined as a correction of r+k times on TEG of more than 50% by the addition of heparinase I. RESULTS: Before incision, patients with ALF showed a significantly greater HLE compared with patients with cirrhosis (r+k time: 66 min corrected to 29 vs 45 min corrected to 32 min, P=0.001). After reperfusion, all the patients showed extensive HLE, without any difference between the two groups. Despite the greater HLE, patients with ALF showed similar TTG compared with the cirrhotic group. By the end of the operation, the extent of the HLE was greatly reduced in both the groups. CONCLUSIONS: Before transplantation, patients with ALF have a greater HLE than patients with liver cirrhosis. However, this did not affect the thrombin generation calculated by TEG and resolved after transplantation.

Spleen enlargement on follow-up evaluation: a noninvasive predictor of complications of portal hypertension in cirrhosis.

BACKGROUND & AIMS: Splenomegaly is observed in most but not all patients with cirrhosis, and has been detected more often in patients showing complications of portal hypertension. We aimed to test the hypotheses that spleen enlarges over time in cirrhosis, and that a progressive enlargement may be associated with portal hypertension-related events. METHODS: A total of 127 cirrhotic patients (Child-Pugh, 6.7 +/- 1.7; range, 5-11), observed at our center and followed-up clinically, endoscopically, and with periodic abdominal ultrasound for at least 1 year, were included. Spleen diameter was recorded at each ultrasound examination. The change of spleen diameter over time was calculated. The occurrence of clinical complications of cirrhosis on follow-up evaluation was recorded. RESULTS: At inclusion, spleen diameter was 14.9 +/- 3.1 cm; 83% of the patients had splenomegaly. Spleen was larger in patients with decompensated disease (n = 39) versus patients with compensated disease (n = 88) (16.1 +/- 3.5 vs 14.5 +/- 2.7; P = .012). The mean follow-up period was 53 +/- 37 months. Spleen progressively enlarged over time (analysis of variance, P < .0001). A total of 46.4% of patients showed a spleen enlargement of 1 cm or more at 1 year. Over 5 years of follow-up evaluation patients showing spleen enlargement showed a higher actuarial probability of esophageal varices formation (84.6% vs 16.6%; P = .001) and growth (63.3% vs 20.6%; P = .001). Among patients with compensated cirrhosis at inclusion, those showing a spleen enlargement had a higher actuarial probability of developing the first clinical decompensation of cirrhosis (51.1% vs 19.5%, P = .002). CONCLUSIONS: Spleen enlargement at follow-up evaluation outlines a subgroup of cirrhotic patients at higher risk of complications of portal hypertension. Noninvasive monitoring of spleen diameter allows a prognostic stratification of cirrhotic patients.

Peliosis hepatis as an early histological finding in idiopathic portal hypertension: A case report.

Peliosis hepatis is a rare condition characterized by dilatation of hepatic sinusoids and blood-filled spaces in the liver mainly observed in subjects exposed to toxic substances or estrogens, which is frequently asymptomatic. Non-cirrhotic idiopathic portal hypertension (NCIPH) is also a vascular disease of the liver rarely observed in European countries, which is usually diagnosed only when the hemorrhagic complications of portal hypertension occur. We report a case of NCIPH in a young Caucasian male who was diagnosed with liver peliosis, showing ultrasonographic and endoscopic signs of portal hypertension four years after. A second biopsy was diagnostic for NCIPH. Even if the pathogenesis remains obscure, peliosis hepatis can be considered as an early sign of vascular disease of the liver, which may progress to more definite conditions.

Diastolic dysfunction and cardiovascular risk in old subjects: possible association with NAFLD?

Non-alcoholic fatty liver disease (NAFLD) is frequently associated with metabolic syndrome (MS) and may represent a cardiovascular (CV) risk factor. Functional cardiac abnormalities have been reported in patients with NAFLD. The aim of this paper is to investigate whether these findings are present also in elderly people. We tested 171 subjects aging more than 65 years, enrolled in a prospective study on CV risk reduction, for laboratory examination, abdominal ultrasound for evaluation of hepatic steatosis and standard echocardiography for determining morphological and functional cardiac parameters. Higher BMI, serum levels of glucose, triglycerides, cholesterol, insulin and visceral adipose tissue and lower serum levels of HDL-cholesterol were significantly associated with NAFLD. Furthermore, subjects with NAFLD had higher prevalence of diabetes, pathological waist-circumference, insulin-resistance and positive ATP-III criteria. While NAFLD had only a borderline significant association with higher end-diastolic thicknesses of left-ventricle posterior wall (edPW) and right-ventricle wall, higher values of edPW and end-diastolic thickness of interventricular septum were significantly correlated with glucose levels above 100mg/dl, hypertension, MS and insulin-resistance. Moreover, subjects with MS and/or pathological waist-circumference had a lower early-diastolic mitral annular motion, whereas those with insulin-resistance had lower E/A ratio and early-diastolic filling peak velocity. Regression analyses identify hypertension and pathological waist-circumference as factors independently associated to pathological edPW, and hypertriglyceridemia to pathological left-ventricle mass. In conclusion, an ultrasonographic diagnosis of NAFLD in old subjects may be an "alert" on the coexistence of multiple CV risk factors and on the presence of possible alterations of cardiac morphology and diastolic function.

Liver hemangioma and vascular liver diseases in patients with systemic lupus erythematosus.

AIM: To investigate whether systemic lupus erythematosus (SLE) is associated with benign focal liver lesions and vascular liver diseases, since these have been occasionally reported in SLE patients. METHODS: Thirty-five consecutive adult patients with SLE and 35 age- and sex-matched healthy controls were evaluated. Hepatic and portal vein patency and presence of focal liver lesions were studied by colour-Doppler ultrasound, computerized tomography and magnetic resonance were used to refine the diagnosis, clinical data of SLE patients were reviewed. RESULTS: Benign hepatic lesions were common in SLE patients (54% vs 14% controls, P < 0.0001), with hemangioma being the most commonly observed lesion in the two groups. SLE was associated with the presence of single hemangioma [odds ratios (OR) 5.05; 95% confidence interval (CI) 1.91-13.38] and multiple hemangiomas (OR 4.13; 95% CI 1.03-16.55). Multiple hemangiomas were associated with a longer duration of SLE (9.9 ± 6.5 vs 5.5 ± 6.4 years; P = 0.04). Imaging prior to SLE onset was available in 9 patients with SLE and hemangioma, showing absence of lesions in 7/9. The clinical data of our patients suggest that SLE possibly plays a role in the development of hemangioma. In addition, a Budd-Chiari syndrome associated with nodular regenerative hyperplasia (NRH), and a NRH associated with hepatic hemangioma were observed, both in patients hospitalized for abdominal symptoms, suggesting that vascular liver diseases should be specifically investigated in this population. CONCLUSION: SLE is associated with 5-fold increased odds of liver hemangiomas, suggesting that these might be considered among the hepatic manifestations of SLE.

Prognostic value of a single HVPG measurement and Doppler-ultrasound evaluation in patients with cirrhosis and portal hypertension.

BACKGROUND: In patients with cirrhosis the onset of clinically significant portal hypertension (CSPH; i.e., hepatic venous pressure gradient (HVPG) ≥ 10 mmHg) is associated with an increased risk of complications. However, most cirrhotic patients already have CSPH at presentation, and limited information is available on further risk stratification in this population. This study assessed the prognostic value of a single HVPG measurement and Doppler-ultrasound (US) evaluation in patients with cirrhosis and CSPH. METHODS: Eighty-six consecutive patients with cirrhosis (73% compensated) and untreated CSPH (mean HVPG 17.8 ± 5.1 mmHg) were included. All were studied by paired HVPG and US, and followed up for a minimum of 12 months (mean 28 ± 20 months). RESULTS: Sixteen (25.3%) patients developed a first decompensation, and 11.6% died on follow-up. HVPG (per 1 mmHg increase OR 1.22, 95% CI 1.05-1.40, p = 0.007) and bilirubin (per 1 mg/ml increase OR 2.42, 95% CI 0.93-6.26, p = 0.06) independently predicted first decompensation, and Model for End-Stage Liver Disease (MELD) score (per 1 point increase OR 1.24, 95% CI 1.03-1.51, p = 0.03) and HVPG (per 1 mmHg increase OR 1.08, 95% CI 1.01-1.26, p = 0.05) independently predicted mortality. The best HVPG cutoff predicting these events was 16 mmHg. Ultrasonographic parameters lacked independent predictive value. The ultrasonographic detection of abdominal collaterals had a high positive likelihood ratio (7.03, 95% CI 2.23-22.16) for the prediction of HVPG ≥ 16 mmHg, implying an increase of the probability of belonging to this higher-risk population from 58 to 91%. CONCLUSIONS: HVPG holds an independent predictive value for first decompensation and death in patients with CSPH. The ultrasonographic detection of collaterals allows the non-invasive identification of patients with HVPG ≥ 16 mmHg, who are at higher risk.

Combined HLA-DR and -DQ disparity is associated with a stable course of ulcerative colitis after liver transplantation for primary sclerosing cholangitis.

Combined disparity of human leukocyte antigen (HLA)-DR and -DQ between mother and fetus is associated with less severe ulcerative colitis (UC) during pregnancy. We evaluated whether donor-recipient HLA disparity after liver transplantation (LT) affects UC in patients with primary sclerosing cholangitis (PSC). Sixty-nine consecutive patients with PSC underwent LT; all underwent colonoscopy before LT; 48 had UC before and 3 had de novo UC after LT. Clinical and laboratory data, activity and treatment of UC, post-LT cytomegalovirus infection, and disparity of HLA-A, -B, -DR, and -DQ for each donor-recipient pair were evaluated. Pre-LT quiescent UC was present in 26 patients. Post-LT UC activity was evaluated in 36 of 51 patients with UC who had not undergone pre-LT colectomy and who had >12 months' post-LT survival. Of these, 16 were stable, 17 had worsened, and 3 had de novo UC. Seven required colectomy (4 for dysplasia or cancer) after LT. Post-LT cytomegalovirus viremia was neither associated with worse UC activity (P = 0.58) nor de novo UC. Disparity with respect to HLA-A, -B, -DR, and -DQ was found in 58%, 27%, 44%, and 39% donor-recipient pairs, respectively. Post-LT UC course was similar with respect to single HLA disparity. However, disparity in none or only one HLA-DR or -DQ was significantly associated with worse activity compared with patients with disparity at both (65% vs. 0%, P = 0.009). Logistic regression found that the disparity for both -DR and -DQ was the only factor statistically significantly associated with post-LT UC activity. We conclude that disparity in both HLA-DR and -DQ between donor and recipient is associated with stable UC activity after LT.

Primary prophylaxis with nadolol in cirrhotic patients: Doppler patterns of splanchnic hemodynamics in good and poor responders.

BACKGROUND/AIMS: We aimed to characterize by echo-color-Doppler the splanchnic hemodynamics of patients good and poor responders to primary prophylaxis with nadolol. METHODS: Thirty cirrhotic patients (Child-score 7.0+/-1.8) with medium/large esophageal varices without previous bleedings were consecutively enrolled. At inclusion and after 3 months of treatment with nadolol, they underwent a splanchnic echo-color-Doppler study and a measurement of hepatic venous pressure gradient (HVPG). RESULTS: Nadolol (60+/-36 mg/day; range 20-160) induced a significant reduction of HVPG (16.6+/-6.1 vs. 19.4+/-4.6 mmHg, P < 0.0001). 13 patients (43.3%) were hemodynamic responders. Responders and Poor-responders had similar baseline clinical characteristics. Poor-responders at baseline were characterized by lower impedance indexes in superior mesenteric artery (SMA) (PI 2.29+/-0.45 vs. 2.74+/-0.46; P = 0.01; RI 0.83+/-0.04 vs. 0.86+/-0.03; P = 0.02), hepatic artery (HA) (PI 1.41+/-0.19 vs. 1.79+/-0.48; P = 0.03; RI 0.71+/-0.05 vs. 0.80+/-0.07; P = 0.02), and splenic artery (SA) (PI 1.18+/-0.27 vs. 1.73+/-0.40; P = 0.01; RI 0.66+/-0.07 vs. 0.73+/-0.09; P = 0.02), and by higher mean flow velocity of HA (52.6+/-21.6 vs. 26.5+/-9.5 cm/s; P = 0.02) and SMA (49.7+/-14.5 vs. 33.9+/-13.1 cm/s; P = 0.06). CONCLUSIONS: Cirrhotic patients poor-responders to nadolol show a pronounced arterial splanchnic vasodilatation at a baseline echo-color-Doppler study. This can be considered a non-invasive clue for the a priori identification of this subgroup of patients.

Plasma total homocysteine and cardiovascular risk in patients submitted to liver transplantation.

Patients submitted to orthotopic liver transplantation (OLT) show an increased rate of cardiovascular events. OLT subjects have high homocysteine (Hcy) levels, but no data are available on the association of Hcy with cardiovascular events. In a cross-sectional analysis, 230 subjects were studied at least 6 months after OLT (159 on cyclosporine, 71 on tacrolimus). Routine laboratory data and total Hcy were recorded, as well as the history of diabetes, hypertension, dyslipidemia, and overweight. Cardiovascular events occurring in a follow-up of 2-36 months were registered. OLT subjects had higher-than-normal Hcy (median 16.7 micromol/L, range 6.1-171.8) without difference between the 2 immunosuppressive agents. The prevalence of Hcy >15 micromol/L was also similar, and significantly correlated with creatinine levels. A total of 28 arterial events occurred in 25 patients during follow-up (11 in coronary arteries, 10 in peripheral arteries, and 7 in splanchnic arteries). Deep vein thromboses occurred in 2 patients, and splanchnic vein thromboses in 4 patients. Cardiovascular events were frequently associated to high Hcy and hypertension. Cox regression analysis showed that high Hcy was significantly associated with arterial events. The risk of any arterial event, coronary artery or peripheral artery event increased by nearly 10% for any increase in Hcy of 5 micromol/L. In conclusion, high Hcy may be involved in the pathogenesis of cardiovascular events in OLT patients. The usefulness of Hcy-lowering therapy remains to be verified.