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Background Portal vein thrombosis is the most common thrombotic complication in cirrhosis. About 60% of anticoagulated patients can achieve recanalization. Despite fondaparinux (FPX) theoretical advantages, data are lacking about safety and efficacy for treatment of portal vein thrombosis in cirrhosis. Methods Cirrhotic patients with portal vein thrombosis treated with FPX or low-molecular-weight heparin (LMWH) were retrospectively included. The extension of thrombosis at baseline and its evolution during anticoagulant treatment were evaluated. Patients were treated with LMWH or FPX at therapeutic dosage and reduction was considered in selected cases. Results There were 124 patients included. Main portal vein branch, splenic, and superior mesenteric veins were involved in 84%, 13%, and 36% of cases, respectively. Forty-one patients (33%) were treated with FPX and 83 (67%) with LMWH. The probability of resolution of thrombosis at 36 months was significantly higher in patients treated with FPX than in those treated with LMWH (77% vs 51%; P = .001), particularly when prescribed at reduced dose. With multivariate analysis, the treatment with FPX (hazard ratio 2.38; P = .002) and use of a full dose (hazard ratio 1.78; P = .035) were independent predictors of portal vein full recanalization. Bleeding rate was higher in patients treated with FPX than in those treated with LMWH (27% vs 13%; P = .06). Conclusions FPX appears to be more effective than LMWH in the treatment of portal vein thrombosis when used at reduced dose, also in complete thrombosis. FPX should be considered among possible treatments for portal vein thrombosis in cirrhosis.

Background: Hepatitis C virus (HCV) infection frequently leads to chronic liver disease, which adversely affects the quality of life (QoL) of the patient. The gender of the patient may be an important variable in the way severity of the disease is perceived. The aim of our study is to evaluate the effect of the gender variable on QoL in HCV-positive patients. Methods: This study included a total of 52 patients (26 men and 26 women) who completed a 1-year follow-up after liver transplantation. QoL was assessed using the SF-36 questionnaire. Results: Male subjects have significantly higher scores on physical role functioning, bodily pain and physical activity compared with females. Females have a better QoL compared to males with regard to the emotional state and mental health. Conclusions: These results show a significant effect of the gender variable on QoL in HCV patients.

The relationship between hepatic encephalopathy (HE) and the sleep-wake disturbances exhibited by patients with cirrhosis remains debated. The aim of this study was to examine the usefulness of sleep-wake interview within the context of HE assessment. One-hundred-and-six cirrhotic patients were asked three yes/no questions investigating the presence of difficulty falling asleep, night awakenings and daytime sleepiness. All underwent formal HE assessment, quantitative electroencephalography and standardised psychometry. Fifty-eight were monitored for 8 ± 6 months in relation to the occurrence of HE. Patients complaining of daytime sleepiness (n = 75, 71 %) had slower EEGs than those who did not report it (relative alpha power: 37 ± 19 vs. 48 ± 17 %, p

Splenic Doppler impedance indices are measurements of splenic congestion in chronic liver disease. It is not known whether they can also assess splenic congestion in patients affected by right-sided or congestive heart failure. We analyzed splanchnic hemodynamics with Doppler ultrasound and systemic hemodynamics with right-sided heart catheterization in patients with heart failure. Splenic pulsatility index (PI) was higher in patients with heart failure (48 patients) compared with healthy subjects (39 patients) (1.19 ± 0.41 vs. 0.73 ± 0.11, p0.0001) and was related to hepatic vein diameter (p = 0.02). Splenic PI was not related to systemic arterial pressure, cardiac output, systemic vascular resistance or splenic arterial resistance, whereas it was related to right atrial mean pressure (p = 0.0003) and to right ventricle end-diastolic pressure (p = 0.011) (34 patients). In conclusion, splenic PI is a measurement of splenic congestion caused by an increase in venous outflow resistance. It can estimate splenic congestion in patients with right-sided or congestive heart failure.

Summary Background : The acute effects of β-blockers may be different from chronic; mechanisms underlying this difference are poorly elucidated. Aim : To assess portal pressure and its pathophysiological determinants after acute and chronic administration of nadolol. Methods : In 24 patients with cirrhosis and portal hypertension hepatic venous pressure gradient, portal blood flow and resistance to portal blood flow were measured before, 60–90 min after acute administration of nadolol, and after 1 month. Patients were good-responders if hepatic venous pressure gradient was ≤12 mmHg, or decreased by at least 20%. Results : Eleven and 13 patients were good- and poor-responders to acute administration, respectively. Acute poor-responders showed a lower decrease in portal blood flow (P = 0.04) and a less evident decrease in mean arterial pressure (P

To prospectively evaluate accuracy and predictive values of Doppler ultrasonographic (US) measurement of portal blood velocity (PBV) and splenic pulsatility index (SPI) in diagnosis of clinically relevant acute rejection in patients with clinicobiochemical hepatic dysfunction after orthotopic liver transplantation (OLT).Study was approved by the institutional review board, and protocol conformed to ethical guidelines of Declaration of Helsinki. Patient informed consent was obtained. In 27 patients with OLT (23 men, four women; mean age, 48 years; range, 27-64 years), PBV and SPI were measured at Doppler US within 48 hours before or after liver biopsy for clinically suspected acute rejection. Biopsy specimens were assigned scores according to Banff method, and rejection activity index (RAI) was calculated. RAI score of 4 or greater was considered clinically relevant acute rejection. Doppler US parameters were analyzed as absolute values and as percentage point changes with respect to values obtained at last examination before rejection was suspected. Information from two Doppler US parameters was combined; Doppler US composite index was calculated. Statistical tests were conducted to assess accuracy, sensitivity, specificity, and predictive values of Doppler US parameters in diagnosis of graft rejection.Clinically relevant acute rejection was diagnosed in nine patients. Median time from OLT until histologic diagnosis of acute rejection was 8 days (range, 5-20 days). Rejection was associated with a marked reduction in mean PBV (-43% +/- 5 [standard error of the mean]) and a slight increase in SPI (+12% +/- 16). The calculated Doppler US composite index was strictly related to severity of rejection (P.001). When applied retrospectively, this index had good accuracy (88%) for prediction of rejection (specificity, 89%; sensitivity, 86%; negative predictive value, 94%).During the first weeks after OLT, a marked decrease in PBV associated with increased SPI supports suspicion of clinically relevant acute rejection.

Information on changes in splanchnic hemodynamics after liver transplantation is incomplete. In particular, data on long-term changes are lacking, and the relationship between changes in arterial and portal parameters is still under debate. The effect of liver transplantation on splanchnic hemodynamics was analyzed with echo-Doppler in 41 patients with cirrhosis who were followed for up to 4 years. Doppler parameters were also evaluated in 7 patients transplanted for acute liver failure and in 35 controls. In cirrhotics, portal blood velocity and flow increased immediately after transplantation (from 9.1 plus minus 3.7 cm/sec to 38.3 plus minus 14.6 and from 808 plus minus 479 mL/min to 2,817 plus minus 1,153, respectively, P

The role of portal-systemic shunting and portal liver hypoperfusion in the pathophysiology of central nervous system dysfunction (CNSD) of cirrhosis is not yet well defined. It is well known that one of the most important collateral vessels (CVs) is a patent paraumbilical vein (PUV), but there is controversy regarding its clinical significance. We have evaluated the relationships between neuropsychological and EEG alterations, ammonia plasma level (NH4), hepatic function, and portal hemodynamics (Doppler Ultrasound) in 95 cirrhotic patients. Patency, diameter, or flow of PUV or the presence of other CVs were not related to an increased prevalence of neuropsychological or EEG abnormalities. Patients with effective portal flow (EPF = portal flow − PUV flow) lower than 692 mL/min (median) had a significantly higher risk of failing the neuropsychological test, or of having an altered EEG. Low EPF and prothrombin time (

The possibility of estimating portal hypertension combining splenic Doppler pulsatility index (PI), which has been shown strictly to be related to portal resistance, and portal blood flow (PBF) was evaluated. Hepatic venous pressure gradient, and splanchnic Doppler parameters were measured in 40 cirrhotic patients. A formula to assess the severity of portal hypertension from Doppler parameters was calculated in a training group of 19 patients, and then this formula was tested to prospectively predict the degree of portal pressure in 21 further patients. In the training group, the regression of portal resistance over splenic PI was calculated and individual values of estimated portal resistance were obtained for every patient of the test group. From them and from observed values of PBF, an estimated value of portal pressure was calculated. The following formula was obtained [(0.066*splenic PI -0.044)*PBF]. In the second group, predicted and observed portal pressure were well correlated (r = 0.71, p = .0003). A good accuracy for the prediction of mild or severe portal hypertension was obtained.

To evaluate the usefulness of routine ultrasonographic (US) evaluation of the hepatic arterial resistive and pulsatility indexes and of the direction of portal venous blood flow for the diagnosis of intrahepatic arterioportal fistulas (APFs) in patients with liver cirrhosis.In all patients with cirrhosis examined at one center over 4 years, the resistive (RI) and the pulsatility (PI) indexes in the right and left branches of the hepatic artery were evaluated with Doppler US. An APF was suspected when an RI decrease of at least 20% and a PI decrease of at least 30% were present in one hepatic lobe relative to values in the other lobe and portal blood flow in the lobe with the decreased values was reversed. The RI and PI in patients with an APF were compared with those in 75 patients with cirrhosis and without APFs at angiography.Seven patients with an APF were identified. APFs suspected at Doppler US were always confirmed with angiography. The percent differences +/- SD in the RI and the PI between the two intrahepatic branches of the hepatic artery in patients with versus in patients without an APF were as follows: RI, 35% +/- 6 (range, 27%-42%) versus 5% +/- 4 (range, 0%-15%) (P:.001); PI, 50% +/- 5 (range, 41%-58%) versus 11% +/- 7 (range, 0%-26%) (P:.001).The intrahepatic arterial resistive and pulsatility indexes and the direction of portal blood flow should be evaluated in routine screening for APFs in patients with liver cirrhosis.

The aim of this work was to study the prevalence of Q-T prolongation in patients with liver cirrhosis and the modifications of the Q-T interval after liver transplantation. Q-T interval corrected for heart rate (QTc) and dispersion of Q-T interval were evaluated in 75 cirrhotic patients and in 24 controls by means of a 12-lead electrocardiogram. In addition, 15 patients were evaluated before and after liver transplantation. Forty-five patients (60%) had a prolonged Q-Tc. Compared with controls, both patients with alcoholic and non alcoholic cirrhosis had increased Q-Tc (414±28 msec1/2, 463±31 and 444±32 respectively; p

The association beta-blockers plus isosorbide-5-mononitrate (I5M) has been proposed for the treatment of portal hypertension in patients with insufficient response to beta-blockers alone, according to hemodynamic criteria. The mechanism of action in these patients is not clearly defined. Fifteen patients with cirrhosis and esophageal varices were evaluated by hepatic venous pressure gradient (HVPG) measurement and duplex-Doppler ultrasonography before and after 1 month of treatment with nadolol. Nine patients who did not exhibit a decrease in HVPG to 12 mm Hg or a percent decrease greater than 20% were classified as poor responders, and were studied again with the same methodology after 3 months of chronic administration of nadolol + I5M 20 mg twice per day. In poor responders, mean HVPG decrease after nadolol was 8.9% +/- 2.8%, and after the combination, it was 25.7% +/- 1.7% (P = .004). All patients except one became good responders to the association. Portal blood flow (PBF) decreased significantly after nadolol (P = .004), and remained unchanged after the addition of nitrates. Resistance to portal blood flow (RPBF) increased after nadolol (P = .02) and returned to baseline values during combined treatment (P = .03). In good responders, an adequate decrease in HVPG was associated with a decrease in PBF (P = .06) but no change in RPBF. A wide spectrum of combined changes in PBF and in RPBF after nadolol was observed in poor responders, ranging from no change in either parameter to a marked decrease in PBF counterbalanced by a marked increase in RPBF. The addition of I5M was followed in most cases by larger effects on resistance than on flow. Doppler parameters were not significantly correlated with the HVPG response to nadolol alone or associated with I5M. It is concluded that good hemodynamic responders to nadolol differ from poor responders in the lack of increase in RPBF after the drug. The addition of nitrates to nadolol is effective in decreasing portal pressure in most poor responders to nadolol alone. A decrease in outflow resistance is the main mechanism involved.

To evaluate the prevalence, severity, and hemodynamic features of nonalcoholic fatty liver disease (NAFLD) in nonobese diabetics.We studied 100 consecutive nonobese (body mass index [BMI] 30) patients with type 1 (n = 17) or type 2 (n = 83) diabetes and no known causes of liver disease. Steatosis was diagnosed and graded with ultrasonography. Digital sonographic images of the liver and right kidney were analyzed with dedicated software (HDI-Lab), and the liver/kidney ratio of grey-scale intensity was calculated as an index of the severity of the steatosis. Severity scores ranging from 0 (none) to 5 (severe) were compared with sonographic and Doppler findings (right liver size, portal vein diameter and flow velocity, hepatic and splenic arterial pulsatility indices, hepatic-vein flow profile and A- and S-wave velocities).The prevalence of steatosis was 24% in type I and 80% in type II diabetes (grade 1 in 17%, grade 2 in 34%, grade 3 in 33%, grade 4 in 9%, grade 5 in 7%). In patients with steatosis (especially those with grades 4-5 disease), hepatic volume was increased (p 0.005). Portal vein diameter was increased in grade 5 steatosis. The hepatic artery pulsatility index was significantly increased, particularly in grades 4 and 5 (p 0.0001); portal and A-wave velocities were significantly reduced in grades 3-5 (p 0.001); and the hepatic vein flow profile was altered in 27% (biphasic: 20%, flat: 7%) patients with steatosis, although there was no correlation with severity.NAFLD is very frequent in nonobese diabetics with type 2 but not type 1 disease, and it is associated with hepatomegaly and liver hemodynamic alterations only when it is severe.Sommario SCOPO: Valutare la prevalenza e la gravità della steatosi nei pazienti diabetici non-obesi e le alterazioni emodinamiche epatiche associate. METODI: Sono stati studiati 100 pazienti diabetici non-obesi (BMI 30 kg/m), 17 di tipo I e 83 di tipo II, privi di cause note di epatopatia. Mediante eco-color-Doppler sono stati valutati: un'immagine digitale di confronto tra fegato e corticale del rene destro, analizzata tramite un programma dedicato per la valutazione del grado di steatosi (rapporto fegato/rene dell'intensità dei grigi), le dimensioni del lobo epatico destro, il calibro della vena porta (PV), la velocità della vena porta (PBV), gli indici di pulsatilità arteriosa epatica (PI-L) e splenica (PI-S), il profilo flussimetrico e la velocità delle onde a (HV-a) e s (HV-s) delle vene sovraepatiche. RISULTATI: La prevalenza di steatosi è stata del 24% nel diabete di tipo I e dell'80% nel tipo II ed è risultata prevalentemente di grado lieve-moderato. Nella steatosi il volume epatico è risultato aumentato (p 0,005), in particolare nei gradi superiori a 3, e il diametro della vena porta è risultato aumentato nel grado 5. Il PI-L è risultato aumentato in tutti i gradi di steatosi, in particolare in quelli di grado 4 e 5 (p 0,0001); la PBV è risultata ridotta nei gradi 3, 4 e 5 (p 0,001); la HV-a è risultata ridotta nei pazienti con grado 3, 4 e 5. Il profilo flussimetrico delle vene sovraepatiche è risultato alterato nel 27% (20% bifasico, 7% appiattito). CONCLUSIONI: La steatosi epatica è un reperto molto frequente nel diabete di tipo II senza obesità ed è associata a epatomegalia e alterazioni emodinamiche epatiche nelle forme più gravi.

Doppler sonographic portal vein parameters are used for the noninvasive evaluation of portal hypertension in cirrhosis. The patency of a paraumbilical vein is a rather frequent finding in cirrhosis, which may affect hepatic hemodynamics and function. We evaluated portal and hepatic arterial parameters in 184 cirrhotic patients with and without a patent paraumbilical vein and the relationships with paraumbilical blood flow. A patent paraumbilical vein was found in 33.7% of patients. The prevalence was higher (56.8%) in Child C patients. Portal blood flow velocity (PBV) (10.8 ± 2.2 vs. 9.8 ± 2.4 cm/sec; P < .01) and volume (PBF) (995.0 ± 383.8 vs. 811.6 ± 318.7 mL/min; P < .001) were significantly higher, and effective portal liver perfusion (PLP) (portal blood flow-paraumbilical blood flow) (621.3 ± 420.8 vs. 811.6 ± 318.7 mL/min; P < .001) was significantly lower in patients with a patent paraumbilical vein than in those without. These differences were more evident in Child C patients (10.7 ± 2.0 vs. 8.3 ± 2.3 cm/sec; 935.7 ± 378.3 vs. 680.6 ± 239.4 mL/min; 369.0 ± 282.0 vs. 680.6 ± 239.4 mL/min). Portal vein diameter, the congestion index (CI) of the portal vein, hepatic arterial resistance indexes, and the severity of esophageal varices did not differ between the two groups. In patients with a patent paraumbilical vein, the Child-Pugh score and the prevalence of ascites were significantly higher than in those without. In conclusion, the evaluation of PBV and PBF in cirrhotic patients can provide misleading results if a paraumbilical vein is patent, underestimating the degree of portal hypertension. The CI and hepatic arterial resistance indexes are not influenced by the paraumbilical vein patency.

Background: Chronic liver disease secondary to hepatitis C virus (HCV) infection is a common clinical problem. HCV is likely to adversely affect the quality of life (QoL) of the patient. This effect is said to be disproportionate to the severity of the disease. The aim of our study was to evaluate QoL in HCV-positive patients focusing both on health status and subjective satisfaction. Methods: Twenty-four patients with combined HCV and alcoholic liver disease (ETOH-HCV) were enrolled in the study. We adopted two generic tools: SF-36 (a health status questionnaire) and SAT-P (a satisfaction profile) for psychological assessment of the patients. SF-36 and SAT-P scores of ETOH-HCV patients were compared with scores of 23 patients with alcoholic liver disease (ETOH). The scores obtained from the study groups were also compared with the reference scores of the healthy Italian population. Results: Both the groups were comparable with respect to age, histological and clinical severity of liver disease (as assessed by MELD and Child Pugh scores). Patients with ETOH-HCV scored less in the vitality and role emotional status domains of the SF-36 scores and the psychological function, social function and free time domains of the satisfaction profile. Conclusions: These results show a significant impact of HCV infection on health status and subjective satisfaction.

Liver transplant recipients are a model of rapid progression of hepatitis C virus (HCV)-related liver disease, from normal to cirrhosis. The aim of the study was the analysis of the relationship between portohepatic hemodynamics and modification in liver histology during the progression of HCV liver disease after transplant. Patients transplanted for HCV cirrhosis were considered for the study. At least every 6-12 months, the portal blood flow velocity, hepatic and splenic pulsatility indices, and a portal hypertensive index (obtained from the combination of the portal blood velocity and splenic pulsatility index) were measured with echo-Doppler. Liver biopsy was performed whenever necessary. The time course of echo-Doppler parameters during the histological progression of the liver disease was analyzed. Posttransplant patients without HCV were included as controls. Forty-nine patients with histology-proven relapse of HCV hepatitis were included in the study. At the onset of recurrent hepatitis, the portal blood flow velocity significantly decreased (P < 0.001), and the splenic pulsatility index increased (P = 0.020), whereas the hepatic pulsatility index remained unchanged. In the following years, in addition to a further slight decrease in the portal blood velocity (P = 0.027), a progressive increase in the hepatic and splenic pulsatility indices was also detected (P = 0.009 and P < 0.0001, respectively). The portal hypertensive index steadily increased with the progression of the disease and was related to the degree of liver fibrosis. In conclusion, the information obtainable from splanchnic Doppler parameters can be used to monitor the progression of liver fibrosis in transplant patients with HCV reinfection.

Portal vein thrombosis (PVT) is a rare cause of portal hypertension. Its diagnosis has been facilitated by improvements in imaging techniques, in particular Doppler sonography. The prevalence is about 1% in the general population, but much higher rates are observed in patients with hepatic cirrhosis (7%, range 0.6-17%), particularly those who also have hepatocellular carcinoma (HCC) (35%). The most common causes of PVT are myeloproliferative disorders, deficiencies of anticoagulant proteins, prothrombotic gene mutations, cirrhosis with portal hypertension, and HCC. Its development often requires the presence of two or more risk factors (local and/or systemic), e.g., a genetically determined thrombophilic state plus an infectious episode or abdominal surgery. It is clinically useful to distinguish between cirrhotic and noncirrhotic forms. Portal vein thrombosis is also traditionally classified as acute or chronic, but this distinction is often difficult. Color Doppler ultrasound is the first-line imaging study for diagnosis of PVT; magnetic resonance angiography and CT angiography are valid alternatives. The main complications are ischemic intestinal necrosis (in acute PVT) and esophageal varices (in chronic cases); the natural history of the latter differs depending on whether or not the thrombosis is associated with cirrhosis. The treatment of choice for PVT has never been adequately investigated. It is currently based on the use of anticoagulants associated, in some cases, with thrombolytics, but experience with the latter agents is too limited to draw any definite conclusions. In chronic thrombosis (even forms associated with cirrhosis), anticoagulant therapy is recommended and possibly, beta-blockers as well. Naturally, treatment of the underlying pathology is essential.SommarioLa trombosi portale rappresenta una causa rara di ipertensione portale che oggi viene diagnosticata con maggior facilità per l'affinamento delle metodiche di imaging, in particolare quelle ecografiche. La prevalenza è dell'1% circa, del 7% (0,6–17%) nella cirrosi epatica, del 35% circa nell'epatocarcinoma. Le cause più comuni di trombosi portale sono: i disordini mieloproliferativi, il deficit di proteine anticoagulanti, le mutazioni geniche protrombotiche, la cirrosi con ipertensione portale, l'epatocarcinoma. Per lo sviluppo di trombosi portale è spesso necessaria la presenza di due o più fattori, locali e sistemici, come uno stato trombofilico su base genetica e un episodio infettivo o un intervento chirurgico addominale. È utile clinicamente dividere la trombosi portale in cirrotica e non-cirrotica. La trombosi portale è inoltre tradizionalmente classificata in acuta e cronica, ma spesso è difficile distinguerle. L'indagine di primo livello per la diagnosi di trombosi portale è rappresentata dall'eco-color-Doppler; in alternativa possono essere usate angio-RM e angio-TC. Le conseguenze della trombosi portale sono rappresentate principalmente dalla necrosi intestinale ischemica nelle forme acute e dalle varici esofagee, che hanno una storia naturale diversa a seconda della presenza o meno di cirrosi, nelle forme croniche. Non vi sono studi adeguati sulla terapia della trombosi portale, che attualmente consiste nell'anticoagulazione, a cui può essere associata la trombolisi, sulla quale non vi è però casistica adeguata. Nella trombosi cronica è indicata l'anticoagulazione, probabilmente anche nella cirrosi, ed eventualmente il beta-bloccante. Ovviamente importante è la terapia della patologia di base.

In cirrhosis, portal hemodynamics is usually considered independently of the disease etiology. The objective of this study was to investigate the role of the etiology of liver disease on the relationship between liver blood flow and liver pathology in endstage cirrhosis.Portal blood velocity and volume, congestion index of the portal vein, and hepatic and splenic pulsatility indices were evaluated with echo-Doppler in cirrhotic patients immediately before liver transplantation. When a patent paraumbilical vein was present, its blood flow was measured and effective portal liver perfusion was calculated as portal blood flow minus paraumbilical blood flow. The hemodynamic parameters were correlated with liver weight and the pattern of the liver fibrosis morphometrically assessed in explanted livers. A total of 131 patients with alcoholic or viral cirrhosis were included in the study.In alcoholic cirrhosis, liver weight was higher than that in viral disease (1246+/-295 g versus 1070+/-254 g, p=0.001), portal liver perfusion per gram of liver tissue was lower (0.49+/-0.36 ml g(-1) min(-1) versus 0.85+/-0.56 ml g(-1) min(-1), p=0.004) and hepatic pulsatility indices were higher (1.45+/-0.31 versus 1.26+/-0.30, p=0.018). The degree of liver fibrosis was similar in alcoholic and viral cirrhosis (11.7+/-5.5% versus 11.0+/-4.4%, p=NS). An inverse relationship between liver weight and Child-Pugh score was disclosed in viral (p0.001) but not in alcoholic disease.A different hemodynamic pattern characterizes the advanced stage of cirrhosis of alcoholic and viral origin. A more severe alteration of intrahepatic portal perfusion, probably coexisting with a more severe hepatocyte dysfunction, and a higher liver weight can be detected in alcoholic cirrhosis.

The hypothesis of thyroid involvement in the haemodynamic alterations of cirrhosis was evaluated. We measured thyroid volume (thrV), free triiodiothyronine (FT3), free thyroxin (FT4), thyroid stimulating hormone (TSH), resistance index (thrRI) and pulsatility index (thrPI) in the inferior thyroid artery in 45 cirrhotic patients of different aetiologies and Child class, and in 13 healthy subjects. Portal vein velocity, flow, diameter and hepatic, splenic, and renal arterial resistance indices were also evaluated. ThrV was increased in Child-C patients (p < 0.05). FT3 was decreased in cirrhotic patients (p < 0.05), TSH and FT4 were not different. ThrPI and thrRI were increased in cirrhotic patients (thrPI: 1.01 +/- 0.15 vs. 0.81 +/- 0.11; thrRI: 0.62 +/- 0.05 vs. 0.53 +/- 0.04; p < 0.01) and were inversely correlated with FT3 (p < 0.05), and directly correlated with hepatic, splenic and renal resistance indices (p < 0.01). In conclusion, thyroid is involved, primarily and secondarily, in the haemodynamic alterations of cirrhosis; a reduction in vasodilator FT3 may play a role in the pathophysiology.

OBJECTIVE: To evaluate endothelial function in type 2 diabetic patients with and without diabetic nephropathy. METHODS: We studied the effects of systemic infusion of the nitric oxide (NO) synthase inhibitor NG-monomethyl-l-arginine (L-NMMA) on cardiovascular and renal hemodynamics in six type 2 diabetic patients with microalbuminuria (D2-MA), six type 2 diabetic patients with normoalbuminuria (D2-NA) and five control subjects. Both type 2 diabetic patients and control subjects had mild arterial hypertension. RESULTS: L-NMMA infusion decreased the cardiac index in all groups. A reduction in glomerular filtration rate (GFR) and an increase in filtration fraction were observed only in controls. Renal plasma flow decreased in controls and D2-NA patients and renal vascular resistance increased in all groups. CONCLUSIONS: The effect of L-NMMA on cardiac output was similar in controls and type 2 diabetic patients with and without diabetic nephropathy. In contrast, the effect on GFR was impaired in both diabetic groups, suggesting that glomerular NO homeostasis is altered in type 2 diabetes. Moreover the discrepancy, in diabetic patients, between cardiac and renal effects during L-NMMA infusion suggests that the modulation of glomerular hemodynamics is independent from NO-regulated cardiac output.

In the prevention of variceal rebleeding, it is already established that hemodynamic response to drug treatment (decrease in hepatic venous pressure gradient [HVPG] to 12 mm Hg or by >20%) is predictive of clinical effectiveness. In primary prophylaxis very few clinical data are available. We assessed the role of the hemodynamic response to beta-blockers or beta-blockers plus nitrates in predicting clinical efficacy of prophylaxis. A total of 49 cirrhotic patients with varices at risk of bleeding, without prior variceal bleeding, were investigated by hepatic vein catheterization before and after 1 to 3 months of chronic treatment with nadolol or nadolol plus isosorbide mononitrate, and were followed during treatment for up to 5 years. A total of 30 patients (61%) were good hemodynamic responders, and among them in 12 (24%) HVPG was

Beta-blockers are currently used for chronic therapy of portal hypertension. Duplex Doppler ultrasonography has been proposed for non-invasive evaluation of splanchnic pharmacodynamics, but the chronic effects of beta-blockers on portal hemodynamics and on splanchnic arterial impedance indices have not been analyzed with this method. This was the aim of the study.The effects of acute (80 mg p.o.) and chronic (2 months at a dosage sufficient to reduce heart rate by at least 25% in respect of basal values) nadolol administration on portal blood flow velocity and volume, and on splanchnic and renal arterial impedance indices [pulsatility index = (peak systolic velocity-minimum velocity)/mean velocity] were evaluated in patients with cirrhosis. Twenty-eight patients with cirrhosis and portal hypertension were investigated. Nineteen patients received nadolol, and nine received placebo.Placebo caused no significant hemodynamic change. Portal blood flow mean velocity decreased after chronic therapy (11.7 +/- 2.9 cm/s to 9.1 +/- 2.3, p0.001). In the 16 patients with acute and chronic evaluation, portal blood flow mean velocity decreased after acute therapy (11.8 +/- 3.0 cm/s to 10.4 +/- 3.0, p0.01), and even more so after chronic therapy (to 9.2 +/- 2.4, p0.01). No parallel was found between acute and chronic effects. Hepatic, mesenteric and splenic pulsatility indices increased after chronic therapy (1.26 +/- 0.33 to 1.39 +/- 0.28, p0.02; 2.04 +/- 0.41 to 2.50 +/- 0.61, p0.01; 0.92 +/- 0.22 to 1.18 +/- 0.27, p0.001 respectively); renal pulsatility index increased (1.12 +/- 0.20 to 1.40 +/- 0.28, p0.001).Chronic therapy with nadolol decreased portal blood flow velocity and volume, and increased splanchnic and renal impedance indices. Chronic effects of nadolol on portal inflow cannot be predicted from its acute effects. Evaluation of the effect of nadolol on portal blood velocity and volume should be performed after chronic therapy. Duplex Doppler ultrasonography allows venous and arterial splanchnic pharmacodynamics to be studied separately.

Doppler sonographic portal vein parameters are used for the noninvasive evaluation of portal hypertension in cirrhosis. The patency of a paraumbilical vein is a rather frequent finding in cirrhosis, which may affect hepatic hemodynamics and function. We evaluated portal and hepatic arterial parameters in 184 cirrhotic patients with and without a patent paraumbilical vein and the relationships with paraumbilical blood flow. A patent paraumbilical vein was found in 33.7% of patients. The prevalence was higher (56.8%) in Child C patients. Portal blood flow velocity (PBV) (10.8 +/- 2.2 vs. 9.8 +/- 2.4 cm/sec; P < .01) and volume (PBF) (995.0 +/- 383.8 vs. 811.6 +/- 318.7 mL/min; P < .001) was significantly higher, and effective portal liver perfusion (PLP) (portal blood flow--paraumbilical blood flow) (621.3 +/- 420.8 vs. 811.6 +/- 318.7 mL/min; P < .001) was significantly lower in patients with a patent paraumbilical vein than in those without. These differences were more evident in Child C patients (10.7 +/- 2.0 vs. 8.3 +/- 2.3 cm/sec; 935.7 +/- 378.3 vs. 680.6 +/- 239.4 mL/min; 369.0 +/- 282.0 vs. 680.6 +/- 239.4 mL/min). Portal vein diameter, the congestion index (CI) of the portal vein, hepatic arterial resistance indexes, and the severity of esophageal varices did not differ between the two groups. In patients with a patent paraumbilical vein, the Child-Pugh score and the prevalence of ascites were significantly higher than in those without. In conclusion, the evaluation of PBV and PBF in cirrhotic patients can provide misleading results if a paraumbilical vein is patent, underestimating the degree of portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Differences in health-related quality of life perception in patients with chronic disease may depend on pre-existing differences in personality profile. The purpose of the study was to investigate in a cohort of female patients with chronic diseases the relationship between the Quality of Life perception and the potential presence of depressive symptoms. Patients and methods Female patients with chronic diseases were enrolled in the study. Exclusion criteria were diagnosis of psychopathological condition, treatment with psychoactive substances. Methodological approach was based on administration of the following test. Short Form health survey SF-36, Symptom Check List SCL-90-R, Satisfaction Profile test (SAT-P) and Beck Depression Inventory-II (BDI-II). The Pearson correlation coefficient was used to evaluate the relationship between depressive symptoms and Quality of life as assessed by psychometric test. Results 57 patients, aged 52(±3,4), responded to inclusion criteria. 57% of patients had a diagnosis of functional dyspepsia or gastro-oesophageal reflux not complicated, and the remaining 43% musculoskeletal diseases. The statistical analysis showed an inverse correlation between the variable Bodily Pain of the SF-36 and the variable Depression scales of the SCL-90-R. In a second phase another sample of female patients was enrolled in the study. 64 patients, aged 49(±3,2), responded to inclusion criteria. Another significant negative correlation was found between the Somatic-Affective factor of the BDI-II and the scale Physical Functioning of the SAT-P. Discussions In female patients with chronic disease depressive symptoms resulted influenced by pain and vice versa. The treatment of depressive symptoms could improve the quality of life of patients.

The spleen plays a pivotal role in the pathogenesis and maintenance of portal hypertension. Few data exist about splenic hemodynamics evaluated by duplex sonography in this condition. Twenty-six normal subjects, 207 patients with portal hypertension of various causes, and in different splenoportal hemodynamic conditions, and 31 patients with liver transplantation were evaluated. In each patient the splenic resistive index (RI = peak systolic--end diastolic velocity/peak systolic velocity) and pulsatility index (PI = peak systolic--end diastolic velocity/mean velocity) were measured. In 17 cirrhotic patients, splenic indices were compared with portal hemodynamics as invasively evaluated by hepatic vein catheterization. In the various groups, RI and PI were respectively: normal subjects, 0.51 +/- 0.05 and 0.72 +/- 0.11; cirrhotic patients with hepatopetal portal blood flow (n = 167), 0.64 +/- 0.08 and 1.03 +/- 0.24; cirrhotic patients with hepatofugal portal flow (n = 3), 0.74 +/- 0.08 and 1.27 +/- 0.08; cirrhotic patients with portal vein thrombosis (n = 9), 0.74 +/- 0.08 and 1.36 +/- 0.34; patients with noncirrhotic obstruction of the portal system (n = 7), 0.69 +/- 0.11 and 1.16 +/- 0.28; cirrhotic patients with surgical decompression of splenic vein system (n = 21), 0.54 +/- 0.07 and 0.76 +/- 0.15; patients with liver transplantation (n = 31), 0.50 +/- 0.08 and 0.70 +/- 0.15. Both RI and PI were significantly higher in cirrhotic patients with hepatopetal portal flow compared with controls (P < .0001), and even higher in cirrhotic patients with portal vein thrombosis (P < .004 and P < .001 in comparison with RI and PI values of cirrhotic patients). In patients with noncirrhotic portal vein thrombosis, splenic impedance indices were higher than those in controls (RI and PI P < .0001). Cirrhotic patients who underwent surgery for the therapy of portal hypertension showed splenic impedance indices significantly decreased compared with other cirrhotic patients (RI and PI P < .0001). In patients who underwent liver transplantation, splenic impedance indices were the same as those in controls. In 23 of the 52 patients surgically treated (surgical shunt or liver transplantation), impedance indices were evaluated both before and after surgical treatment. All these patients showed a decrease in splenic impedance indices (RI and PI, P < .0001) after surgical treatment. RI and PI values were higher in patients with large esophageal varices as compared with patients without or with small varices (P < .02 and P < .01). RI and PI values were not related to age, mean arterial pressure, sex, Child-Turcotte-Pugh score, presence of ascites, or cause. A significant correlation was found between splenic impedance indices and portal resistance as evaluated by hepatic vein catheterization (r = .80, P < .001 for RI values; r = .87, P < .001 for PI values). In conclusion, this study shows that splenic impedance indices are increased in cirrhotic patients, and seems to demonstrate that in patients with cirrhosis these indices reflect portal vein blood flow resistance.

AIM: To investigate the agreement and prognostic value of different measures of covert hepatic encephalopathy (CHE). METHODS: One-hundred-and-thirty-two cirrhotic outpatients underwent electroencephalography (EEG), paper-and-pencil psychometry (PHES) and critical flicker frequency, scored on the original/modified (CFFo/CFFm) thresholds. Eighty-four patients underwent Doppler-ultrasound to diagnose/exclude portal-systemic shunt. Seventy-nine were followed-up for 11 ± 7 mo in relation to the occurrence of hepatic encephalopathy (HE)-related hospitalisations. RESULTS: On the day of study, 36% had grade I HE, 42% abnormal EEG, 33% abnormal PHES and 31/21% abnormal CFFo/CFFm. Significant associations were observed between combinations of test abnormalities; however, agreement was poor (Cohen’s κ < 0.4). The prevalence of EEG, PHES and CFFo/CFFm abnormalities was significantly higher in patients with grade I overt HE. The prevalence of EEG and CFFm abnormalities was higher in patients with shunt. The prevalence of EEG abnormalities was significantly higher in patients with a history of HE. During follow-up, 10 patients died, 10 were transplanted and 29 had HE-related hospitalisations. Grade I HE (P = 0.004), abnormal EEG (P = 0.008) and abnormal PHES (P = 0.04) at baseline all predicted the subsequent occurrence of HE; CFF did not. CONCLUSION: CHE diagnosis probably requires a combination of clinical, neurophysiological and neuropsychological indices.

Objectives Differences in health-related quality of life (HR-QoL) perception between alcohol-abusing and non-substance-dependent subjects with liver cirrhosis could depend on differences in personality profile and influence management of patients awaiting liver transplant. Methods We compared the perceptions of disease state in 78 male patients of similar disease severity divided into 2 groups based on etiology of cirrhosis: 47% had alcoholic cirrhosis, and 53% had hepatitis C virus (HCV)-related cirrhosis without alcohol abuse. Patients’ perception of disease state was determined using the SAT-P questionnaire (a self-administered questionnaire that provides a global assessment of perceived HR-QoL and subjective well-being). The assessment yields 2 scales: an analytic scale based on 32 variables and a synthetic scale based on 5 factors. Results In patients with alcohol-related disease, “psychological function” was found to be more impaired, while “sleep, diet, and free time” was less impaired compared with subjects with HCV-related cirrhosis, suggesting dysfunction related to substance abuse with personality disturbance. Conclusions The perception of disease state is different in alcohol-abusing patients with cirrhosis compared with those with cirrhosis unrelated to alcohol.