Two-dimensional shear wave elastography with propagation-based reliability assessment for grading hepatic fibrosis and portal hypertension.

BACKGROUND: The aim of the present study was to examine the diagnostic ability of two-dimensional shear wave elastography (2D-SWE) with propagation-based reliability for grading of hepatic fibrosis and portal hypertension. METHODS: This prospective study (UMIN000022838) consisted of 135 subjects. Phase I (n = 40) examined the effect of standard deviation (SD)/median as the reliability criterion of 2D-SWE, and phase II (n = 95) compared the diagnostic ability of 2D-SWE under the best SD/median value and transient elastography (TE). RESULTS: Phase I reported 0.49 as a best cut-off SD/median value. In phase II, the elasticity showed a correlation between the 2D-SWE and TE (r = 0.88, P < 0.001). The area under the receiver operating characteristic curve (AUROC) was comparable between the 2D-SWE and TE (0.936 and 0.948 for chronic hepatitis, P = 0.34; 0.939 and 0.956 for cirrhosis, P = 0.25). The hepatic venous pressure gradient showed a positive correlation with the 2D-SWE (r = 0.435, P = 0.043) and TE (r = 0.378, P = 0.083) in 22 patients. The AUROC was comparable between the 2D-SWE (0.844 for ≥10 mmHg, 0.838 for ≥12 mmHg) and TE (0.781 for ≥10 mmHg, P = 0.484; 0.800 for ≥12 mmHg, P = 0.589). CONCLUSIONS: 2D-SWE is promising for the assessment of the grade of hepatic fibrosis and portal hypertension, with the SD/median value as a reliability criterion.

Non-Invasive Diagnosis of Portal Hypertensive Gastropathy: Quantitative Analysis of Microbubble-Induced Stomach Wall Enhancement.

The aim of the study described here was to elucidate the efficacy of contrast-enhanced ultrasound (CEUS) prospectively as a tool in the diagnosis of portal hypertensive gastropathy (PHG). The peak enhancement time at the upper stomach wall (PT) and intensity ratio at the upper stomach/the spleen (IR) between pre- and peak enhancement were evaluated by CEUS with perflubutane microbubble agent in 56 patients, 42 with cirrhosis (16 with PHG) and 14 controls. The IR was higher in patients with PHG (1.21 ± 0.11) than in those without (0.91 ± 0.15, p < 0.05) and the controls (0.78 ± 0.11, p < 0.01), although PT did not differ between these groups. The area under the receiver operating characteristic curve for IR was 0.8199 in the presence of PHG, with the best cutoff value of 0.94, sensitivity 65.9%, specificity 72.6%, positive predictive value 62.2%, negative predictive value 73.1% and accuracy 70.4%. CEUS may have potential as a less invasive tool for diagnosis of PHG in patients with cirrhosis.

Portal response related to shunt occlusion by balloon-occluded retrograde transvenous obliteration may determine the prognosis of cirrhosis.

AIM: To determine the prognostic effect of portal hemodynamic responses after balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices (GV) in cirrhosis patients. METHODS: This retrospective study consisted of 37 cirrhosis patients (aged 62.5 ± 9.7 years) with medium- or large-grade GV treated with B-RTO. Portal hemodynamic response was assessed by the changes in flow volume in the portal trunk (PFV, mL/min) before and after the treatment. Group I showed increased PFV and group II showed no increase in PFV. The median observation period was 49.8 months (range, 4.7-150.3 months). RESULTS: All patients showed complete embolization of GV without any recurrence. There were 30 patients in group I and 7 patients in group II (decreased PFV in 6 and unchanged PFV in 1). The PFV at baseline was significantly lower in the former (583.5 ± 232.0 mL/min) than in the latter (880.7 ± 345.9 mL/min; P = 0.009). The survival rate was significantly lower in group II (83.3% at 1 year and 66.7% at 3 years) than in group I (96.7% at 1 year, 81.5% at 3 years, and 61.8% at 5 years; P = 0.012). The incidence of deterioration of the esophageal varices was 18/30 (60%) in group I and 5/7 (71.4%; P = 0.687) in group II. Multivariate analysis identified only no increase in portal response (hazard ratio, 8.086; P = 0.005) as an independent factor for poor prognosis. CONCLUSION: Balloon-occluded retrograde transvenous obliteration for GV may result in a poor prognosis when portal hemodynamics shows no increase in portal response.

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 (0.46­fold), 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.

Hemodynamic effect of the left gastric artery on esophageal varices in patients with cirrhosis.

BACKGROUND: To examine the hemodynamic effect of the left gastric artery (LGA) on the esophageal varices (EV) in cirrhosis. METHODS: This was a prospective study performed in 48 cirrhosis patients (35 men, 13 women; median age 61.6 ± 11.3 years, range 38-83 years) with EV (medium 35, large 13), who underwent selective LGA angiography, hepatic venous catheterization, endoscopic ultrasonography (EUS) and Doppler ultrasonography before endoscopic treatment for EV. Angiographic findings including diameter of the main trunk, detection time of EV, and mild/severe degree of peripheral staining were assessed. The median period of post-treatment observation was 17.1 months. RESULTS: LGA angiograms were successfully obtained in 45/48 patients. EV were demonstrated in 45/45 patients, with a mean detection time of 6.9 s (2-21), which was longer in patients with variceal recurrence (7.0 s) than in those without (5.6 s, P = 0.480). The staining was mild in 25 patients (55.6 %) and severe in 20 patients (44.4 %), and portal hypertensive gastropathy was more frequent in the latter (13/20, 65.0 %) than in the former (7/25, 28.0 %, P = 0.013). Multivariate analysis showed that pre-treatment detection time (P = 0.04) and post-treatment submucosal vascular area at the cardia wall by EUS (P = 0.036) were significant factors for variceal recurrence. No other factors, including hepatic venous pressure gradient and Doppler parameters, showed significant relationships with the variceal recurrence. CONCLUSIONS: The hemodynamics in the LGA may act as an initiator of variceal formation, showing close linkage with variceal recurrence, and independent of portal pressure.

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

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 63.7 ± 11.3 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 (p < 0.001) at baseline was the significant factor for the presence of decompensation. Higher alanine transaminase (p = 0.020), lower albumin (p = 0.002) and lower mean velocity in the portal trunk (p = 0.038) were significant factors for developing decompensation (best cut-off value: Alanine transaminase > 31 IU/L, albumin < 3.6 g/dL, and portal trunk < 12.8 cm/s). The cumulative incidence of decompensation was higher in patients with portal trunk < 12.8 cm/s (22.5% at 1 year, 71.2% at 5 years) than those without (6.9% at 1 year, 35.4% at 5 years; p < 0.001). The significant prognostic factors were hepatocellular carcinoma (p = 0.036) and lower albumin (p = 0.008) for compensated patients, and reversed portal flow (p = 0.028), overt ascites (p < 0.001), and higher bilirubin (p < 0.001) for decompensated patients. CONCLUSION: Portal hemodynamics offer a non-invasive marker for decompensation and prognosis of cirrhosis, suggesting a future direction for practical management.

Well-tolerated portal hypertension and favorable prognosis in adult patients with extrahepatic portal vein obstruction in Japan.

AIM: To evaluate the clinical features and prognoses in adult patients with extrahepatic portal vein obstruction (EHO) from the aspect of portal hypertension during the last 20 years in Japan. METHODS: There were 40 EHO patients (aged 21-77 years; mean ± standard deviation [SD], 54.6 ± 15.0). Clinical findings and prognoses were examined retrospectively during the median observation period of 71.6 months. RESULTS: Twenty-two patients (55%) showed positive signs of portal hypertension; 18 with esophageal varices (F0, one; F1, eight; F2, nine), two with gastric varices (F1, one; F2, one) and seven with mild ascites. Multivariate analysis showed that platelet count and spleen size were significant factors for the presence of gastroesophageal varices, with odds ratios of 0.989 (95% confidence interval [CI], 0.980-0.997; P = 0.011) for platelet count and 1.003 (95% CI, 1.001-1.005; P = 0.003) for spleen size. Ten of 20 patients with gastroesophageal varices received primary prophylaxis and only one patient (10%) showed variceal recurrence. The cumulative overall survival rate was 100% at 1 year, 94.2% at 3-7 years and 68.7% at 10 years. The cumulative survival rates did not differ between the patients with and without gastroesophageal varices, with and without ascites, and patterns of portal cavernoma at baseline. CONCLUSION: Forty-five percent of adult EHO patients in Japan were free from signs of portal hypertension, and platelet count and spleen size are predictive for identifying patients with gastroesophageal varices. EHO patients with gastroesophageal varices show favorable prognoses comparable to those without, if primary/secondary prophylaxis was performed appropriately.

Role of contrast-enhanced ultrasonography with Sonazoid for hepatocellular carcinoma: evidence from a 10-year experience.

Hepatocellular carcinoma (HCC) represents primary liver cancer. Because the development of HCC limits the prognosis as well as the quality of life of the patients, its management should be properly conducted based on an accurate diagnosis. The liver is the major target organ of ultrasound (US), which is the simple, non-invasive, and real-time imaging method available worldwide. Microbubble-based contrast agents are safe and reliable and have become popular, which has resulted in the improvement of diagnostic performances of US due to the increased detectability of the peripheral blood flow. Sonazoid (GE Healthcare, Waukesha, WI, USA), a second-generation contrast agent, shows the unique property of accumulation in the liver and spleen. Contrast-enhanced US with Sonazoid is now one of the most frequently used modalities in the practical management of liver tumors, including the detection and characterization of the nodule, evaluation of the effects of non-surgical treatment, intraoperative support, and post-treatment surveillance. This article reviews the 10-year evidence for contrast-enhanced US with Sonazoid in the practical management of HCC.

Eradication of esophageal varices by sclerotherapy combined with argon plasma coagulation: Effect of portal hemodynamics and longitudinal clinical course.

BACKGROUND AND AIM: To demonstrate the effect of endoscopic injection sclerotherapy (EIS) with argon plasma coagulation (APC) as a primary/secondary prophylaxis for esophageal varies (EV) on portal hemodynamics and long-term outcomes in cirrhosis. METHODS: This prospective study included 48 cirrhotic patients (64.5 ± 11.4 years; 26 bleeders, 22 non-bleeders). Post-treatment outcomes (EIS and APC; median observation period, 12.8 months for recurrence and 21.1 months for prognosis) were evaluated with respect to the findings of hepatic venous catheterization, Doppler ultrasound, and endoscopic ultrasonography (EUS). RESULTS: All patients showed EV eradication after endoscopic treatment, and a decreased frequency of a patent left gastric vein (pre: 83.3%, post: 27.1%, P < 0.001). However, hepatic venous pressure gradient (HVPG, mmHg) remained unchanged after the treatment, pre: 16.1 ± 3.6, post: 15.6 ± 3.8 (P = 0.269). Cumulative variceal recurrence/rebleeding rates were 25.5%/5.6% and 62.4%/23.1% at 1 and 3 years, respectively. Post-treatment EUS finding, area of submucosal vessels in the cardia ≥12 mm2 was the only significant factor for variceal recurrence (hazard ratio 9.769, 95% confidence interval 3.046-31.337; P < 0.001). Cumulative recurrence rate was significantly higher in patients with area of submucosal vessels in the cardia ≥12 mm2 (58.3% at 1 year and 100% at 3 years) than in those without (11.4% at 1 year and 40.9% at 3 years, P < 0.001). Cumulative overall survival rates were 95.2% and 71.9% at 1 and 3 years, respectively, showing no significant relationship with HVPG. CONCLUSION: EIS with APC for EV is unlikely to have a significant influence on portal pressure.

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.

Reversed portal flow: Clinical influence on the long-term outcomes in cirrhosis.

AIM: To elucidate the natural history and the longitudinal outcomes in cirrhotic patients with non-forward portal flow (NFPF). METHODS: The present retrospective study consisted of 222 cirrhotic patients (120 males and 102 females; age, 61.7 ± 11.1 years). The portal hemodynamics were evaluated at baseline and during the observation period using both pulsed and color Doppler ultrasonography. The diameter (mm), flow direction, mean flow velocity (cm/s), and mean flow volume (mL/min) were assessed at the portal trunk, the splenic vein, the superior mesenteric vein, and the collateral vessels. The average values from 2 to 4 measurements were used for the data analysis. The portal flow direction was defined as follows: forward portal flow (FPF) for continuous hepatopetal flow; bidirectional flow for to-and-fro flow; and reversed flow for continuous hepatofugal flow. The bidirectional flow and the reversed flow were classified as NFPF in this study. The clinical findings and prognosis were compared between the patients with FPF and those with NFPF. The median follow-up period was 40.9 mo (range, 0.3-156.5 mo). RESULTS: Twenty-four patients (10.8%) demonstrated NFPF, accompanied by lower albumin level, worse Child-Pugh scores, and model for end-stage liver disease scores. The portal hemodynamic features in the patients with NFPF were smaller diameter of the portal trunk; presence of short gastric vein, splenorenal shunt, or inferior mesenteric vein; and advanced collateral vessels (diameter > 8.7 mm, flow velocity > 10.2 cm/s, and flow volume > 310 mL/min). The cumulative incidence rates of NFPF were 6.5% at 1 year, 14.5% at 3 years, and 23.1% at 5 years. The collateral vessels characterized by flow velocity > 9.5 cm/s and those located at the splenic hilum were significant predictive factors for developing NFPF. The cumulative survival rate was significantly lower in the patients with NFPF (72.2% at 1 year, 38.5% at 3 years, 38.5% at 5 years) than in those with forward portal flow (84.0% at 1 year, 67.8% at 3 years, 54.3% at 5 years, P = 0.0123) using the Child-Pugh B and C classifications. CONCLUSION: NFPF has a significant negative effect on the prognosis of patients with worse liver function reserve, suggesting the need for careful management.

Hyponatremia: a significant factor in a poor prognosis for cirrhosis with Child A/B after variceal eradication.

BACKGROUND: To identify prognostic factors prospectively in cirrhosis after the eradication of esophageal varices (EV). METHODS: There were 52 cirrhosis patients (Child-Pugh A 24, B 28) who showed the eradication of EV after the endoscopic sclerotherapy (median observation period, 25.5 months). RESULTS: Eighteen patients showed a recurrence of EV. The cumulative overall survival rate was 92.2% at 1 year, 70.9% at 3 years, and 47.2% at 5 years. Univariate analysis showed that serum sodium concentration (hazard ratio [HR] 0.724, P = 0.0006), serum aspartate transaminase (HR 1.019, P = 0.0075), serum alanine transaminase (HR 1.025, P = 0.0239), and serum creatinine (HR 11.311, P = 0.044) levels before treatment were significant factors for a poor prognosis. Multivariate analysis revealed that serum sodium concentration (HR 0.711, P = 0.0022) was the only significant factor. The cumulative survival rate was lower in patients with hyponatremia (<135 mEq/l, a best cut-off value; 83.3% at 1 year, and 33.3% at 3 years), than in those without (93.3% at 1 year, 77.3% at 3 years and 47.2% at 5 years). CONCLUSIONS: Pre-treatment hyponatremia is a significant prognostic factor in cirrhosis with Child A/B after the eradication of EV by the endoscopic sclerotherapy.

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

Cirrhosis 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 age ± standard deviation, 62.5 ± 11.8 years; age range, 20-89 years) and 14 IPH patients (3 males and 11 females; mean age ± standard deviation, 64.2 ± 6.6 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 (P = 0.36). Deterioration of ascites in patients showing mild ascites at baseline was found in 32.4% of cirrhosis patients and 42.9% of IPH patients (P = 0.41). Serum creatinine (mg/dl) at baseline was significantly higher in IPH patients who developed ascites (n = 2, 0.74 ± 0.14) than in those who did not (n = 5, 0.526 ± 0.06, P = 0.029). The overall survival rate appeared to favor IPH (100% at 1 year, 92.9% at 3 and 5 years; P = 0.2) 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, P = 0.04) 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.

Relationship and interaction between serum sodium concentration and portal hemodynamics in patients with cirrhosis.

BACKGROUND AND AIM: To examine the relationship between hyponatremia and portal hemodynamics and their effect on the prognosis of cirrhosis. METHODS: Portal hemodynamic parameters measured by Doppler ultrasound and serum sodium concentrations were examined in 153 cirrhosis patients (mean age 62.2 ± 12.0 years; median observation period, 34.1 m). RESULTS: Study participants included 16 patients with hyponatremia (Na < 135 mEq/L), who showed a significantly greater frequency of possessing a splenorenal shunt (SRS; P = 0.0068), and 137 patients without hyponatremia. Serum sodium concentrations were significantly lower in patients with SRS than in those without (P = 0.0193). An increased prothrombin time-international normalized ratio was a significant predictive factor for developing hyponatremia a year later (8/96; Hazard ratio 14.415; P = 0.028). The cumulative survival rate was significantly lower in patients with hyponatremia (46.7% at 1 and 3 years) than in those without (91.8% at 1 year, 76.8% at 3 years; P < 0.001). The cumulative survival rate was significantly lower in patients who had developed hyponatremia after 1 year (100% at 1 year, 62.5% at 3 years) than those who had not (100% at 1 year, 89.0% at 3 years; P < 0.001). The cumulative survival rate was significantly worse in patients with both hyponatremia and SRS (20% at 1 year). CONCLUSIONS: There was a close linkage between the serum sodium concentration and portal hemodynamic abnormality, presence of SRS, and their interaction may negatively influence the prognoses in cirrhosis.

Liver Stiffness: A Significant Relationship with the Waveform Pattern in the Hepatic Vein.

The aim of this prospective study was to assess the relationship between liver stiffness and hepatic vein waveform patterns in 42 patients with chronic hepatitis and 55 with cirrhosis. Liver stiffness measurement (LSM) values (FibroScan, Echosens, Paris, France) were significantly lower in the triphasic pattern group (11.3 ± 8.4 kPa) than in the monophasic pattern (32.5 ± 23.5 kPa, p = 0.001) and biphasic pattern (25.6 ± 18.1 kPa, p = 0.001) groups, indicating no significant relationship with portal pressure. The ability to diagnose cirrhosis represented by the highest area under the receiver operating characteristic curve was 0.921 (83.6% sensitivity, 90.5% specificity, best cutoff value: 16.9 kPa) by LSM and 1.000 (best cutoff value: 19.4 kPa) by LSM combined with the monophasic pattern. This study revealed a close linkage between liver stiffness and hepatic vein waveform findings, resulting in a better understanding of hepatic vein hemodynamics and wider application of its analysis.

Retrograde detection of the intrahepatic portal vein in primary biliary cirrhosis: is sinusoidal blockage the underlying pathophysiology?

OBJECTIVE: The aim of this study was to explore the underlying pathophysiological mechanism for portal hypertension in primary biliary cirrhosis (PBC) using radiological findings. PATIENTS AND METHODS: The study included 10 patients with PBC (Scheuer stage I, one patient; stage II, two patients; and cirrhosis, seven patients) and 29 patients with viral cirrhosis. Both groups underwent Doppler ultrasound and hepatic venous catheterization. The Doppler data, pressure data, and vascular enhancement findings were compared between the groups. RESULTS: Hemodynamics in the portal trunk and hepatic vein upon Doppler sonography did not differ between patients with viral cirrhosis, cirrhotic PBC, and noncirrhotic PBC. The hepatic venous pressure gradient (mean±SD) was 225.5±77.1 mmH2O (range 125-445 mmH2O) in viral cirrhosis, 224.6±39.5 mmH2O (range 170-262 mmH2O) in cirrhotic PBC, and 41.3±7.4 mmH2O (range 33-47 mmH2O) in noncirrhotic PBC, being significantly higher in viral cirrhosis and cirrhotic PBC than noncirrhotic PBC (P=0.0005). The intrahepatic portal vein was detected in a retrograde manner on the hepatic venogram in 29/29 (100%) patients with viral cirrhosis (all with gastroesophageal varices), 7/7 (100%) patients with cirrhotic PBC (5/7 with gastroesophageal varices), and 3/3 (100%) patients with noncirrhotic PBC (none with gastroesophageal varices). The presence of veno-venous communication was found in 15/29 (51.7%) patients with viral cirrhosis, 6/7 (85.7%) patients with cirrhotic PBC, and 3/3 (100%) patients with noncirrhotic PBC. CONCLUSION: The study suggested that sinusoidal blockage is the underlying pathophysiology even in the early-stage PBC, proved by the visible intrahepatic portal vein in three noncirrhotic PBC patients, and veno-venous communication in the liver is responsible for alleviated hepatic venous pressure gradient.

Influence of splenorenal shunt on long-term outcomes in cirrhosis.

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.

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

OBJECTIVE: The objective was to examine the effect of splenic circulation using a microbubble agent to assess the severity of portal hypertension. METHODS: This prospective study consisted of 91 subjects (63.0 ± 12.6 years, 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. RESULTS: The MCT and PET showed significant differences between cirrhosis (5.7 ± 1.8; 14.6 ± 3.0) and controls (4.0 ± 1.9, p < 0.0001; 8.9 ± 2.3, p < 0.0001), respectively. However, only PET offered positive correlations with wedged hepatic venous pressure (r = 0.4648, p = 0.0001) and HVPG (r = 0.4573, p = 0.0001). The area under the receiver operating characteristics curve to identify HVPG ≥ 10 mmHg, and 12 mmHg was 0.76 and 0.76, respectively. CONCLUSIONS: The microbubble-based non-invasive assessment of the splenic circulation is effective to identify the severity of portal hypertension presumably by reflecting congestion of splenic venous flow due to increased portal venous pressure.

Potential stagnation in the splanchnic hemodynamics demonstrated by the dynamic microbubbles in chronic liver disease.

BACKGROUND AND AIM: Impaired splanchnic hemodynamics are well-documented phenomena in cirrhosis. However, comprehensive hemodynamic features from the superior mesenteric artery (SMA) to the superior mesenteric vein (SMV) via intestinal capillaries have not been studied. The aim was to examine splanchnic hemodynamics and their relationship with clinical presentations. METHODS: Contrast-enhanced ultrasound was performed for both the SMA and SMV under fasting conditions and postprandially following ingestion of a liquid diet. The microbubble traveling time (MTT) was determined as the difference between the contrast onset in the SMA and SMV, indicating the time required for microbubble transit through the splanchnic circulation. RESULTS: There were 192 subjects for fasting conditions (81 cirrhosis, 72 chronic hepatitis, 39 healthy controls), and 74/192 for postprandial conditions (44 cirrhosis, 11 chronic hepatitis, 19 healthy controls). The MTT (fasting; postprandial) was significantly longer in cirrhosis (7.7 ± 2.9 s; 7.0 ± 0.3 s) than in controls (5.4 ± 2.3 s, P < 0.001; 3.9 ± 0.9 s, P<0.001) and chronic hepatitis (6.3 ± 2.5 s, P=0.007; 5.1 ± 1.4 s, P=0.013). The MTT ratio (postprandial/fasting) showed disease-related changes: 0.75 ± 0.20 in controls, 0.78 ± 0.15 in chronic hepatitis, and 1.00 ± 0.28 in cirrhosis (P=0.003, vs controls; P=0.036, vs chronic hepatitis). CONCLUSIONS: The real-time observation of traveling microbubble on the sonogram revealed a prolonged transit with a weak postprandial response in the intestinal circulation, suggesting better understanding of underlying pathophysiology of splanchnic hemodynamics in chronic liver disease.