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.

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.

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.

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.

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.

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.

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.

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.

Saline-enhanced ultrasonography: prediction of X-ray appearance of hepatic venography in patients with cirrhosis.

OBJECTIVE: To examine the efficacy of saline-enhanced ultrasound (US) in predicting the X-ray appearance of hepatic venography. MATERIALS AND METHODS: This prospective study consisted of 50 cirrhosis patients (31 males and 19 females; mean age, 64.2±11.1 years). US patterns in the liver, after injection of agitated saline via balloon-occluded catheter, were evaluated with respect to the findings of CO2-enhanced hepatic venogram. RESULTS: US demonstrated two patterns: type I showing positive parenchymal enhancement (40 patients) and type II showing negative parenchymal enhancement with detection of hepatic vein (10 patients). There were also two patterns shown by hepatic venography: type A showing retrograde detection of intrahepatic portal vein (41 patients) and type B showing hepatic venous enhancement via intrahepatic venous-venous communications with no detection of intrahepatic portal vein (9 patients). All patients with type I showed retrograde detection of intrahepatic portal vein via hepatic sinusoid on X-ray venograms (type A). Of the 10 patients with type II, nine showed type B and one showed type A. Sensitivity and specificity of type I US pattern to predict the detection of intrahepatic portal vein on the venogram were 100% and 90%, respectively. There was no significant difference in hepatic venous pressure gradient or wedged hepatic venous pressure between patients with type I and type II. CONCLUSIONS: Saline-enhanced US is effective in predicting the findings of hepatic venogram. As type II strongly suggests the shunt-modified venogram, image taking in these cases would be superfluous with the added advantage of avoiding unnecessary radiation exposure.

Natural history of postvascular-phase iso-enhanced lesions on the sonogram in chronic liver diseases.

BACKGROUND AND AIM: This study examined the natural history of postvascular-phase iso-enhanced lesions (PIELs) on contrast-enhanced sonograms to determine the potential risk and predictive factors for developing hepatocellular carcinoma (HCC) in chronic liver diseases. METHODS: This prospective study included 87 PIELs on contrast-enhanced sonograms (postvascular-phase: 10 min post-injection of perflubutane microbubbles) in 72 patients with chronic liver diseases (45 males and 27 females; age 65.0 ± 10.8y; PIEL diameter 12.5 ± 4.2 mm). The PIELs were followed up by ultrasound/contrast-enhanced ultrasound, computed tomography, or magnetic resonance imaging at 3 to 6 months intervals. RESULTS: Twenty patients developed HCCs during the study period (median, 22.0 months). The cumulative risk of HCC occurrence was 7.9% at 1 year and 36.0% at 3 years. The presence of coexistent HCC (hazard ratio [HR], 4.975; 95% confidence interval [CI], 1.729-14.316; P = 0.003) and alpha-fetoprotein > 20 ng/mL (HR, 4.104; 95% CI, 1.621-10.392; P = 0.003) were significant factors for the risk of HCC occurrence. Fourteen of these lesions were diagnosed as HCCs that developed from iso-enhanced lesions. Cumulative HCC occurrence rates from PIEL > 14 mm was 23.5% at 1 year and 46.3% at 3 years. Cox regression analysis showed that PIEL > 14 mm (HR, 6.780; 95% CI, 2.060-22.32; P = 0.002) and alpha-fetoprotein > 20 ng/mL (HR, 4.892; 95% CI, 1.559-15.350; P = 0.007) were statistically significant factors for HCC occurrence. CONCLUSIONS: Patients with coexistent HCC, alpha-fetoprotein > 20 ng/mL, or PIEL > 14 mm should be carefully monitored because of the high potential for HCC occurrence.

Similarities and differences in the clinical features between cardia varices and esophageal varices.

BACKGROUND AND AIM: Little is known about the clinical features of cardia varices (CV). The aim was to examine the background, bleeding risk, and post-treatment outcomes of CV in patients with portal hypertension. METHODS: The subjects of this retrospective study were 277 patients (179 males, 98 females, 62.9 ± 11.5 years) with esophageal varices (EV). In patients with CV, there were 65 bleeders, and 95 patients received endoscopic treatment for primary or secondary prophylaxis. RESULTS: There were 147 patients with CV (53.1%). The higher grade of EV (P < 0.01) and the lower grade of gastric fundal varices (FV) (P = 0.046) were significant factors for the presence of CV. Significant risk factors for bleeding were: the higher grade of EV (P < 0.01), red sign on EV (P < 0.01), lower albumin (P = 0.01), and Child-Pugh B/C (P < 0.01) for EV and red sign on CV (P < 0.01) and use of non-steroidal anti-inflammatory drugs (NSAIDs)/aspirin (P < 0.01) for CV. All CV disappeared by sclerotherapy combined with argon plasma coagulation or band ligation, and 20 patients (21.1%) in EV and 18 patients (18.9%) in CV had recurrences during the median observation period of 19.4 months. There was no significant difference in the cumulative survival rate between non-bleeders, bleeders from EV, and those from CV. CONCLUSIONS: The CV were closely associated with advanced grade of EV and less-advanced grade of FV. Further, usage of NSAIDs/aspirin and red sign were significantly related to the bleeding from CV, suggesting the need for careful management.

Linoleate appears to protect against palmitate-induced inflammation in Huh7 cells.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) may protect against metabolic diseases. Although the benefits of the n-3 family of PUFA have been well investigated in nonalcoholic steatohepatitis (NASH), little is known about the effect of the n-6 family. This study examined the effect of linoleate, a member of the n-6 family, on regulation of the palmitate-induced inflammatory cytokine interleukin-8 (IL8) in hepatocytes. METHODS: Huh7 cells and HepG2 cells were cultured with and without free fatty acid treatment (palmitate and linoleate, alone or in combination, 100-1000 µM). Inflammatory pathways, lipid accumulation, apoptosis and cell viability were monitored. RESULTS: Dose- and time-related changes of IL8 mRNA expression were examined and 9 h treatment with 500 µM palmitate showed the greatest elevation of IL8. Co-treatment with 500 µM palmitate and 400 µM linoleate significantly suppressed IL8 production below that with palmitate alone in both cells (both mRNA and protein). A quantitative measurement for lipid accumulation showed no significant difference between palmitate-treated cells (1.69 ± 0.21), linoleate-treated cells (1.61 ± 0.16) and palmitate and linoleate-treated cells (1.73 ± 0.22, NS, n = 7). The co-treatment with 400 µM linoleate inhibited phospho-c-Jun N-terminal kinase (pJNK) activation and IkBα reduction caused by 500 µM palmitate treatment. Treatment with 400 µM linoleate alone led to IL8 production (5.48 fold change), similar to co-treatment, with no influence on the expression of pJNK/IkBα. The cell viability was similar between treatment with 500 µM palmitate and with both 500 µM palmitate and 400 µM linoleate, showing no significant changes in the expression of cleaved caspase-3. CONCLUSIONS: Linoleate is a potent regulator of the proinflammatory cytokine IL8 via the JNK and nuclear factor kappa B pathways that are involved in the pathophysiology of NASH, suggesting a future recommendation of dietary management.

Effects of inferior mesenteric vein flow in patients with cirrhosis.

BACKGROUND & AIMS: The 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. METHODS: We 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. RESULTS: IMV 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. CONCLUSIONS: In 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.

Pretreatment microbubble-induced enhancement in hepatocellular carcinoma predicts intrahepatic distant recurrence after radiofrequency ablation.

OBJECTIVE: The purpose of this study is to examine whether pretreatment findings in hepatocellular carcinoma (HCC) using contrast-enhanced ultrasound can predict local or distant recurrence after radiofrequency ablation (RFA). SUBJECTS AND METHODS: Subjects of the prospective study were 54 patients with HCC lesions treated by RFA. Intensity differences between lesion and liver parenchyma at early arterial (4 seconds) and peak enhancement times and washout at late phase were provided on contrast-enhanced sonograms with perflubutane microbubble agent. The pretreatment findings were examined with respect to intrahepatic local and distant recurrence. RESULTS: Univariate analysis showed that intensity differences at the early arterial time (hazard ratio [HR], 2.2; 95% CI, 1.0-4.6; p = 0.042) and lesion frequency (HR, 2.3; 95% CI, 1.0-5.0; p = 0.044) were risk factors for distant recurrence. Multivariate analysis showed that intensity differences at the early arterial time (HR, 2.7; 95% CI, 1.2-5.8; p = 0.014) and lesion frequency (HR, 2.9; 95% CI, 1.3-6.5; p = 0.015) were risk factors for distant recurrence. The cumulative distant recurrence rate for patients with intensity differences at the early arterial time was greater at less than 10 dB than at 10 dB or higher (33.3% and 91.3% vs 23.9% and 65.1% at 1 and 2 years, respectively; p = 0.035). The cumulative distant recurrence rate was 16.5% and 61.1% at 1 and 2 years, respectively, in patients with solitary lesions and 54.7% and 77.4% at 1 and 2 years, respectively, in patients with multiple lesions (p = 0.0296). No pretreatment findings were predictive for local recurrence. CONCLUSION: HCC lesions with gradual enhancement in the early arterial time displayed potential distant recurrence risk after RFA, requiring careful posttreatment surveillance.

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.

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.

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.