Evaluating the effectiveness of a geostatistical approach with groundwater flow modeling for three-dimensional estimation of a contaminant plume.

When assessing the risk from an underground environment that is contaminated by radioactive nuclides and hazardous chemicals and planning for remediation, the contaminant plume distribution and the associated uncertainty from measured data should be estimated accurately. While the release history of the contaminant plume may be unknown, the extent of the plume caused by a known source and the associated uncertainty can be calculated inversely from the concentration data using a geostatistical method that accounts for the temporal correlation of its release history and groundwater flow modeling. However, the preceding geostatistical approaches have three drawbacks: (1) no applications of the three-dimensional plume estimation using concentration data from multiple depths in real situations, (2) no constraints for the estimation of the plume distribution, which can yield negative concentration and large uncertainties, and (3) few applications to actual cases with multiple contaminants. To address these problems, the non-negativity constraint using Gibbs sampling was incorporated into the geostatistical method with groundwater flow modeling for contaminant plume estimation. This method was then tested on groundwater contamination in the Gloucester landfill in Ontario, Canada, using three-dimensional contaminant transport model and concentration data from multiple depths. The method was applied to three water soluble organic contaminants: 1,4-dioxane, tetrahydrofuran, and diethyl ether. The effectiveness of the proposed method was verified by the general agreement of the calculated plume distributions of the three contaminants with concentration data from 66 points in 1982 (linear correlation coefficient of about 0.7). In particular, the reproduced peak of 1,4-dioxane corresponding to the large disposal in 1978 was more accurate than the result of preceding minimum relative entropy-based studies. The same peak also appeared in the tetrahydrofuran and diethyl ether distributions approximately within the range of the retardation factor derived from the fraction of organic carbon.

Effects of Early Initiation of Solid Versus Liquid Diet after Endoscopic Submucosal Dissection on Quality of Life and Postoperative Outcomes: A Prospective Pilot Randomized Controlled Trial.

BACKGROUND/AIMS: Feeding recommendations after endoscopic submucosal dissection (ESD) for gastric neoplasms are not established and based on clinical experience. METHODS: This was a prospective pilot randomized controlled trial. Patients undergoing ESD for gastric neoplasms were randomly assigned to solid (n = 50) or liquid diet (n = 50) groups. Beginning the day after hemostasis confirmation until discharge, the solid diet group started on a diet of rice porridge, whereas the liquid diet group started on a liquid diet, with gradual transition to solid food. The primary endpoint was delayed bleeding rate. The secondary endpoints were quality of life (QOL), ulcer-stage, hospital fees, and post-ESD symptoms. RESULTS: Delayed bleeding occurred in the solid diet group (2%) but not in the liquid diet group. The QOL evaluation using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-STO22 showed better score in the solid diet group. The patients who felt dietary restriction at discharge was of a larger number in the liquid diet group (p = 0.019). More patients experienced appetite loss (p = 0.038), constipation (p = 0.022), and dietary restriction (p = 0.037) in the liquid diet group during hospitalization. The other endpoints were equivalent between the groups. CONCLUSION: Early initiation of solid foods after ESD is feasible and associated with higher QOL, potentially rendering conventional liquid diets unnecessary, although additional studies are needed (Trial registration number: UMIN000013297).

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.

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.

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.

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.

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.

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.

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.

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.

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.