Takayuki Kondo

Sonographic and clinical features of collateral vessels at the splenic hilum in cirrhosis

AIMnTo examine the sonographic features of shunt vessels derived from the splenic vein at splenic hilum (SS), and explore the relationship between the SS pattern and clinical presentations.nnnMATERIALS AND METHODSnThis prospective study in cirrhotic patients consisted of study I (n = 15), which compared the anatomical features of SS at ultrasonography versus angiography, and study II (n = 233), which examined the incidence/haemodynamics of SS and SS-related presentations.nnnRESULTSnStudy I showed that SS1 (running toward the upper pole of the spleen) corresponded to short gastric veins, and SS2 (running toward the lower pole of the spleen) corresponded to splenorenal/retroperitoneal shunts. In study II, SS were detected in 47.6% of patients (111/233), SS1 in 77.5% (86/111), SS2 in 17.1% (19/111), and SS3 (both SS1 and SS2) in 5.4% (6/111). The incidence of gastric cardia varices was significantly higher in patients with SS2 (6/19) than in those with SS1 (8/86, p = 0.0097), whereas the incidence of gastric fundal varices was significantly higher in patients with SS1 (44/86) than in those with SS2 (1/19, p = 0.00025) or SS3 (0/6, p = 0.015). There was no difference in the incidence of oesophageal varices among the three SS groups. The Child-Pugh score and grade of ascites was significantly worse in patients with SS3 than in those with SS1 (p < 0.0001, p = 0.0009). Hepatic encephalopathy grade was significantly worse in patients with SS2 (p = 0.0047) or SS3 (p < 0.0001) compared to SS1.nnnCONCLUSIONnThe SS pattern facilitates estimation of the possible manifestations, indicating the direction of clinical management of cirrhosis patients. Potential poor liver function is noted in patients with SS3.

Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease

The aim was to examine the effect of free fatty acids on the regulation of PPARγ-PGC1α pathway, and the effect of PPARγ/PGC1α in NAFLD. The mRNA and protein expression of PGC1α and phospho/total PPARγ were examined in Huh7 cells after the palmitate/oleate treatment with/without the transfection with siRNA against PGC1a. The palmitate content, mRNA and protein expression of PGC1α and PPARγ in the liver were examined in the control and NAFLD mice. Palmitate (500 μM), but not oleate, increased protein expression of PGC1α and phospho PPARγ (PGC1α, 1.42-fold, P=0.038; phospho PPARγ, 1.56-fold, P=0.022). The palmitate-induced PPARγ mRNA expression was reduced after the transfection (0.46‑fold), and the protein expressions of PGC1α (0.52-fold, P=0.019) and phospho PPARγ (0.43-fold, P=0.011) were suppressed in siRNA-transfected cells. The palmitate (12325.8 ± 1758.9 μg/g vs. 6245.6 ± 1182.7 μg/g, p=0.002), and mRNA expression of PGC1α (11.0 vs. 5.5, p=0.03) and PPARγ (4.3 vs. 2.2, p=0.0001) in the liver were higher in high-triglyceride liver mice (>15.2 mg/g) than in low-triglyceride liver mice (<15.2 mg/g). The protein expressions of both PGC1α and PPARγ were higher in the NAFLD group than in the controls (PGC1α, 1.41-fold, P=0.035; PPARγ, 1.39-fold, P=0.042), and were higher in the high-triglyceride liver group (PGC1α, 1.52-fold, p=0.03; PPARγ, 1.22-fold, p=0.05) than in the low-triglyceride liver group. In conclusion, palmitate appear to up-regulate PPARγ via PGC1α in Huh7 cells, and both PGC1α and PPARγ are up-regulated in the NAFLD mice liver, suggesting an effect on lipid metabolism leading to intrahepatic triglyceride accumulation.

Influence of splenorenal shunt on long-term outcomes in cirrhosis

Abstract Objective. To examine the clinical effect of splenorenal shunt (SRS) on the long-term outcomes in patients with cirrhosis. Methods. The study consisted of 162 cirrhosis patients (male 85, female 77; 62.6 ± 11.7 years). The clinical findings and prognosis were examined with respect to portal hemodynamics including collateral vessel patterns, with or without the presence of SRS or short gastric vein (SGV). Median observation period was 30 months. Results. The incidence was 18.5% for SRS and 10.5% for SGV. Decompensated cirrhosis was significantly more frequent in patients with SRS (22/30) than those with SGV (5/17, p = 0.0034), and in patients with SRS >5.5 mm (14/15) or >95 ml/min (14/15) (both, median values) than those with SRS <5.5 mm (8/15, p = 0.013) or <95 ml/min (8/15, p = 0.013). Cumulative overall survival rate was 87.4% at 1 year, 73.4% at 3 years, and 59.1% at 5 years. There was no significant difference in the cumulative survival rate according to the development of SRS: 80% at 1 year, 66.6% at 3 years, and 58.3% at 5 years in patients with SRS; 94.1% at 1 year, 87.4% at 3 years, and 72.8% at 5 years in patients with SGV; 88.3% at 1 year, 73.1% at 3 years, and 58% at 5 years in patients without SGV/SRS; 94.1% at 1 year, 87.4% at 3 years, and 72.8% at 5 years in patients with SGV (overall, p = 0.2). Conclusion. In spite of no significant effect on the prognosis in cirrhosis, careful management may be necessary for the patients with SRS because of potential poor liver function demonstrated by the close linkage between the presence of SRS and decompensation.

Differential Clinical Impact of Ascites in Cirrhosis and Idiopathic Portal Hypertension.

AbstractCirrhosis and idiopathic portal hypertension (IPH) are 2 major diseases showing portal hypertension. However, characteristics and outcomes of IPH with ascites have not yet been determined. The aim of the study was to examine the influence of ascites on the long-term clinical course of IPH.This observational study compared the long-term clinical findings including portal hemodynamics demonstrated by Doppler ultrasonography between 166 cirrhosis (87 males and 79 females; mean ageu200a±u200astandard deviation, 62.5u200a±u200a11.8 years; age range, 20–89 years) and 14 IPH patients (3 males and 11 females; mean ageu200a±u200astandard deviation, 64.2u200a±u200a6.6 years; age range, 51–78 years). Both groups comprised of consecutive patients from November 2007 through February 2013 and were studied retrospectively. The median observation period was 33.4 months for ascites and 34.5 months for survival.Ascites was detected in 60/166 (36.1%) and 116/166 (69.9%) cirrhosis patients and in 7/14 (50%) and 9/14 (64.3%) IPH patients, at baseline and at the end of the observation period, respectively. The cumulative incidence of ascites was 12.3% at 1 year, 35.9% at 3 years, and 59.9% at 5 years in cirrhosis, and 25% at 3 years, and 50% at 5 years in IPH (Pu200a=u200a0.36). Deterioration of ascites in patients showing mild ascites at baseline was found in 32.4% of cirrhosis patients and 42.9% of IPH patients (Pu200a=u200a0.41). Serum creatinine (mg/dl) at baseline was significantly higher in IPH patients who developed ascites (nu200a=u200a2, 0.74u200a±u200a0.14) than in those who did not (nu200a=u200a5, 0.526u200a±u200a0.06, Pu200a=u200a0.029). The overall survival rate appeared to favor IPH (100% at 1 year, 92.9% at 3 and 5 years; Pu200a=u200a0.2) more than cirrhosis (87.7% at 1 year, 75.2% at 3 years, and 63.6% at 5 years), but did not reach statistical significance. However, in patients with ascites at baseline, the survival rate was significantly better in IPH (100% at 1, 3, and 5 years, Pu200a=u200a0.04) than in cirrhosis (69.1% at 1 year, 43% at 3 years, 34.4% at 5 years).The presence of ascites at baseline correlated with worse survival rates in patients with cirrhosis as compared to those with IPH as the underlying etiology.

Impact of splenic circulation: non-invasive microbubble-based assessment of portal hemodynamics

AbstractObjectiveThe objective was to examine the effect of splenic circulation using a microbubble agent to assess the severity of portal hypertension.MethodsThis prospective study consisted of 91 subjects (63.0u2009±u200912.6xa0years, 30–86; 60 males, 31 females), 62 cirrhosis and 29 controls, who underwent both Doppler ultrasound and contrast-enhanced ultrasound with a perflubutane microbubble agent. Two microbubble-based parameters for splenic circulation, the minimum circulation time (MCT, s) and the peak enhancement time (PET, s), were assessed with respect to the hepatic venous pressure gradient (HVPG) and other clinical findings.ResultsThe MCT and PET showed significant differences between cirrhosis (5.7u2009±u20091.8; 14.6u2009±u20093.0) and controls (4.0u2009±u20091.9, pu2009<u20090.0001; 8.9u2009±u20092.3, pu2009<u20090.0001), respectively. However, only PET offered positive correlations with wedged hepatic venous pressure (ru2009=u20090.4648, pu2009=u20090.0001) and HVPG (ru2009=u20090.4573, pu2009=u20090.0001). The area under the receiver operating characteristics curve to identify HVPGu2009≥u200910xa0mmHg, and 12xa0mmHg was 0.76 and 0.76, respectively.ConclusionsThe microbubble-based non-invasive assessment of the splenic circulation is effective to identify the severity of portal hypretension presumably by reflecting congestion of splenic venous flow due to increased portal venous pressure.Key Points• There is a potential link between splenic circulation and portal hypertension.n • Microbubble-based assessment of splenic circulation is predictive of the severity of portal hypertension.n • Interobserver variability was sufficient in the assessment of splenic enhancement sonograms.

Effects of Inferior Mesenteric Vein Flow in Patients With Cirrhosis

BACKGROUND & AIMSnThe inferior mesenteric vein (IMV) is detected in more than 90% of computed tomography images. Little is known about the hemodynamic features of IMV as a collateral vessel in portal hypertension, or its effects in clinical presentation and outcome. We investigated the roles of the IMV in portal hemodynamics, clinical presentation, and outcomes of patients with cirrhosis.nnnMETHODSnWe performed a prospective study of 467 patients with cirrhosis (274 men; age, 64.6 ± 10.9 y). We assessed hemodynamics in the IMV using Doppler sonography and compared these data with patients clinical presentation and patient outcome.nnnRESULTSnIMV was detected in 94 patients (20.1%); 51 patients had hepatopetal flow, 33 patients had hepatofugal flow, and 10 patients had to-and-fro flow. Those with hepatofugal flow had a significantly greater number of ascites than those with hepatopetal flow, higher Child classification (P = .004), and a higher incidence of decompensated liver (51.5% vs 27.5%; P = .015) and rectal varices (56.3% vs 13.3%; P = .013). The incidence of gastroesophageal varices was lower among those with hepatofugal flow (51.5%; P = .005) or to-and-fro flow (40%; P = .008) than those with hepatopetal flow (80.4%). IMV had similar effects after adjustment for liver function. There were no differences in the cumulative rates of survival during the median 17.2 months of follow-up evaluation, when the patients with and without IMV were stratified by Child classification.nnnCONCLUSIONSnIn patients with cirrhosis, hepatofugal flow of the IMV appears to increase the risk of ascites and liver decompensation but reduce the risk for gastroesophageal varices. Although IMV is associated with reduced liver function, it does not affect survival.

INTENSITY-BASED ASSESSMENT OF MICROBUBBLE-ENHANCED ULTRASONOGRAPHY: PHASE-RELATED DIAGNOSTIC ABILITY FOR CELLULAR DIFFERENTIATION OF HEPATOCELLULAR CARCINOMA

This prospective study aimed to elucidate the effect of phase-related quantitative parameters of contrast-enhanced ultrasound (CEUS) with perflubutane microbubble agent to assess the cellular differentiation of hepatocellular carcinoma (HCC). Intensity was analyzed in 94 lesions (19.4 ± 4.9 mm, 86 patients), 47 well-differentiated HCCs (wHCCs) and 47 moderately-differentiated HCCs (mHCCs): I(e) (early phase) = I(te) (tumor) - I(le) (liver), I(p) (post-vascular phase) = I(tp) (tumor) - I(lp) (liver), I(ep) = I(e) - I(p). The area under the receiver operating characteristic curve with the best cutoff value (I(e), 13.2, I(p), -4.5, I(ep), 21.3) for discriminating between wHCC and mHCC was 0.6922 for Ie, 0.7680 for Ip and 0.7925 for Iep, which indicated a significantly greater ability to differentiate between wHCC and mHCC compared with visual/qualitative assessment (early phase, 0.6170, p = 0.04; post-vascular phase, 0.6702, p = 0.01; both phases, 0.7021, p = 0.04). In conclusion, I(ep) was found to have the highest diagnostic ability, suggesting it is a promising parameter for the cellular differentiation of HCCs with CEUS.

Hepatic filling rate of a microbubble agent: a novel predictor of long-term outcomes in patients with cirrhosis.

The aim of the study described here was to evaluate the significance of the hepatic filling rate of a perflubutane microbubble agent in predicting long-term outcomes and prognoses in 32 patients with cirrhosis (37-76 y, 20 females, Child-Pugh A16, B16). The time from delivery of the contrast agent to the hepatic artery to maximum enhancement of the liver parenchyma on the sonogram was defined as the hepatic filling rate (mean = 18.6 s). Hepatic filling rate did not correlate significantly with the Child-Pugh score or the model for end-stage liver disease score. However, the survival rate was lower (93.3% at 1 y, 60.2% at 3 y) and the rate of occurrence of hepatocellular carcinoma (HCC) was higher (13.3% at 1 y, 33.3% at 3 y) in the group with the slow filling rate (≥18 s) than in the group with the rapid filling rate (<18 s) (93.3% at 1 and 3 y for survival, 6.3% at 1 and 3 y for HCC occurrence). Hepatic filling rate may constitute a non-invasive marker for the occurrence of HCC and prognosis of cirrhosis.

Influence of paraumbilical vein patency on the portal hemodynamics of patients with cirrhosis.

Goals/Background: The aim was to determine the influence of the paraumbilical vein (PUV) patency and its effect on the portal hemodynamics and clinical presentations in cirrhotic patients. Study: In this prospective study of 181 cirrhotic patients (101 males, 80 females; aged 62.6±11.8 y), the portal hemodynamics were assessed using Doppler ultrasonography. Results: The incidence of patent PUV was 26.0% (47/181). The mean flow volume in the portal trunk, the incidence of a left gastric vein with hepatofugal flow, and the grade of the esophageal varices were significantly higher in the patients with a patent PUV (908.2 mL/min, 70.2%, 9 with none to small, and 27 with medium to large, respectively) than in those without (771.7 mL/min, 48.5%, 57 with none to small, and 48 with medium to large, respectively). The hepatic venous pressure gradient and the wedged hepatic venous pressure (mm H2O) were significantly higher in the former group (268.0±89.7 and 389.5±99.9, respectively) than in the latter (203.5±63.2 and 317.7±67.7, respectively). The deterioration of ascites during the 2-year follow-up period was significantly more often in the patients with a patent PUV (4/12, 33.3%) than in those without. The cumulative survival rates at 1, 2, and 3 years were similar between the 2 groups: 92.5%, 92.5%, and 82.4%, respectively, in the former and 90.7%, 83.8%, and 76.3%, respectively, in the latter. Conclusions: A patent PUV seems to signify pressure-loaded portal hemodynamics in cirrhotic patients. However, it seems to have little effect on their prognoses.

Impact of portal hemodynamics on Doppler ultrasonography for predicting decompensation and long-term outcomes in patients with cirrhosis

Abstract Objective: Significance of portal hemodynamics for non-invasive marker of cirrhosis remains unclear. The aim was to determine the value of portal hemodynamics on Doppler ultrasound for predicting decompensation and prognosis in cirrhosis. Methods: This retrospective study comprised 236 cirrhotic patients (132 males, 104 females; age 63.7u2009±u200911.3 years; 110 compensated, 126 decompensated). Clinical data, including Doppler findings, were analyzed with respect to decompensation and prognosis. The median follow-up period was 33.2 months (0.1–95.4). Results: Fifty-three patients developed clinical decompensation, 13 patients received liver transplantation, and 71 died. Higher model for end-stage liver disease score (pu2009<u20090.001) at baseline was the significant factor for the presence of decompensation. Higher alanine transaminase (pu2009=u20090.020), lower albumin (pu2009=u20090.002) and lower mean velocity in the portal trunk (pu2009=u20090.038) were significant factors for developing decompensation (best cut-off value: Alanine transaminaseu2009>u200931 IU/L, albuminu2009<u20093.6 g/dL, and portal trunku2009<u200912.8u2009cm/s). The cumulative incidence of decompensation was higher in patients with portal trunku2009<u200912.8u2009cm/s (22.5% at 1 year, 71.2% at 5 years) than those without (6.9% at 1 year, 35.4% at 5 years; pu2009<u20090.001). The significant prognostic factors were hepatocellular carcinoma (pu2009=u20090.036) and lower albumin (pu2009=u20090.008) for compensated patients, and reversed portal flow (pu2009=u20090.028), overt ascites (pu2009<u20090.001), and higher bilirubin (pu2009<u20090.001) for decompensated patients. Conclusion: Portal hemodynamics offer a non-invasive marker for decompensation and prognosis of cirrhosis, suggesting a future direction for practical management.