Hepatic Vein Catheterization Research Articles

Similar insulin regulation of splanchnic FFA and VLDL-TG in men with nonalcoholic hepatic steatosis and steatohepatitis

This study aimed to determine whether obese men with nonalcoholic fatty liver disease (NAFLD) display differences between those with simple steatosis versus steatohepatitis (NASH) in splanchnic and hepatic FFA and VLDL-triglycerides (VLDL-TG) balances. The study involved 17 obese men with biopsy-proven NAFLD (9 with NASH and 8 with simple steatosis). We used hepatic vein catheterization in combination with [3H]palmitate and [14C]VLDL-TG tracers to measure splanchnic palmitate and VLDL-TG uptake and release rates during basal and hyperinsulinemic conditions. Indocyanine green was used to measure splanchnic plasma flow. Splanchnic palmitate uptake was similar in the two groups and significantly reduced during hyperinsulinemia (NASH: 62 (48–77) versus 38 (18–58) μmol/min; simple steatosis: 62 (46–78) versus 45 (25–65) μmol/min, mean (95% CI), basal versus clamp periods, respectively, P = 0.02 time-effect). Splanchnic palmitate release was also comparable between groups and nonsignificantly diminished during hyperinsulinemia. The percent palmitate delivered to the liver originating from visceral adipose tissue lipolysis was similar and unchanged by hyperinsulinemia. Splanchnic uptake and release of VLDL-TG were similar between groups. Hyperinsulinemia suppressed VLDL-TG release (P <0.05 time-effect) in both groups. Insulin-mediated glucose disposal was similar in the two groups (P = 0.54). Obese men with NASH and simple steatosis have similar splanchnic uptake and release of FFA and VLDL-TG and a similar proportion of FFA from visceral adipose tissue lipolysis delivered to the liver. These results demonstrate that the splanchnic balances of FFA and VLDL-TG do not differ between obese men with NASH and those with simple steatosis.

Transfemoral hepatic vein catheterization reduces procedure time in double vein embolization

BackgroundDouble vein embolization with simultaneous embolization of the portal and hepatic vein aims to grow the future liver remnant in preparation for major hepatectomy. Transvenous hepatic vein embolization is usually done via a transjugular access. The purpose of this study is to describe the transfemoral approach as an alternative option and to discuss potential advantages.ResultsTwenty-three patients undergoing hepatic vein embolization via a transjugular (n = 10) or transfemoral access (n = 13) were evaluated retrospectively. In all cases the portal vein embolization was done first. All procedures were technically successful. There were no peri-interventional complications. Only two patients were not able to proceed to surgery. Standardized future liver remnant hypertrophy was non-inferior with the transfemoral approach compared to the transjugular route. Procedure time was significantly shorter in the transfemoral access group (40 ± 13 min) compared to the transjugular group (67 ± 13 min, p < 0.001).ConclusionTransfemoral hepatic vein embolization is feasible, safe, and faster due to easier catheterization, improved stability, and simpler patient preparation. These findings will need to be validated in larger studies.

Disturbances of Ruminal Microbiota and Liver Inflammation, Mediated by LPS and Histamine, in Dairy Cows Fed a High-Concentrate Diet.

The ecosystem of ruminal microbiota profoundly affects the health and milk production of dairy cows. High-concentrate diets are widely used in dairy farms and evoke a series of metabolic disorders. Several studies have reported the effects of high-concentrate diets on the ruminal microbiome, while the effect of changes in ruminal microbial flora, induced by high-concentrate diet feeding, on the liver of dairy cows has not been studied before. In this study, 12 mid-lactating Holstein Friesian cows (weight of 455 ± 28 kg; parities of 2.5 ± 0.5; starting milk yield of 31.59 ± 3.2 kg/d; DMI of 21.7 ± 1.1 kg/d; and a DIM at the start of the experiment of 135 ± 28 d) were fitted with ruminal fistulas, as well as with portal and hepatic vein catheters. All cows were randomly divided into 2 groups; then, they fed with low-concentrate diets (LC, concentrate: forage = 40:60) and high-concentrate diets (HC, concentrate: forage = 60:40) for 18 weeks. The forage sources were corn silage and alfalfa hay. After the cows of two groups were euthanized over two consecutive days, ruminal microbiota; the concentration of LPS in the rumen content; cecum content; the levels of blood and histamine in rumen fluid, blood, and the liver; the histopathological status of the rumen and cecum; and the inflammatory response of the liver were assessed in dairy cows under conditions of subacute ruminal acidosis (SARA). These conditions were caused by high-concentrate diet feeding. All data were analyzed using the independent t-test in SPSS. The results showed that high-concentrate diet feeding increased the concentration of LPS and histamine in the rumen and plasma of veins (p < 0.05). The abundance of Bacteroidetes at the phylum level, and of both Bacteroidetes and Saccharibacteria at the genus level, was decreased, while the abundance of Firmicutes at the phylum level and Oscillibacter at the genus level was increased by high-concentrate diet feeding. The decreased pH values of ruminal contents (LC = 6.02, HC = 5.90, p < 0.05) and the increased level of LPS in the rumen (LC = 4.921 × 105, HC = 7.855 × 105 EU/mL, p < 0.05) and cecum (LC = 11.960 × 105, HC = 13.115 × 105 EU/mL, p < 0.01) induced the histopathological destruction of the rumen and cecum, combined with the increased mRNA expression of IL-1β (p < 0.05). The histamine receptor H1R and the NF-κB signaling pathway were activated in the liver samples taken from the HC group. In conclusion, the elevated concentrations of LPS and histamine in the gut may be related to changes in the ruminal microbiota. LPS and histamine induced the inflammatory response in the ruminal epithelium, cecum epithelium, and liver. However, the cause-effect mechanism needs to be proved in future research. Our study offers a novel therapeutic strategy by manipulating ruminal microbiota and metabolism to decrease LPS and histamine release and to improve the health of dairy cows.

Insulin regulation of regional lipolysis in upper-body obese and lean humans.

Upper-body obesity (UBO) results in insulin resistance with regards to free fatty acid (FFA) release; how this differs by fat depot and sex between adults with UBO and lean adults is unknown. We tested the hypothesis that insulin suppression of FFA release from the splanchnic bed, leg fat, and upper-body nonsplanchnic (UBNS) adipose tissue would be impaired in UBO. Fourteen volunteers with UBO (7 men and 7 women) and 14 healthy volunteers with normal weight (7 men and 7 women) participated in studies that included femoral artery, femoral vein, and hepatic vein catheterization. We then measured leg and splanchnic plasma flow as well as FFA kinetics (using isotopic tracers) under overnight fasting as well as low- and high-dose insulin infusion using the insulin clamp technique. We found the expected insulin resistance in UBO; the most quantitatively important difference between adults with UBO and lean adults was greater FFA release from UBNS adipose tissue when plasma insulin concentrations were in the postprandial, physiological range. There were obesity, but not sex, differences in the regulation of splanchnic FFA release and sex differences in the regulation of leg FFA release. Reversing the defects in insulin-regulated UBNS adipose tissue FFA release would have the greatest effect on systemic FFA abnormalities in UBO. These studies were supported by the US Public Health Service (grants DK45343 and DK40484), the Novo Nordic Foundation (grant NNF18OC0031804 and NNF16OC0021406), and the Independent Research Fund Denmark (grant 8020-00420B).

Effect of beta-blockers on multiple haemodynamics in cirrhosis: A cross-over study by MR-imaging and hepatic vein catheterization.

Non-selective beta-blockers (NSBB) are widely used in the treatment of patients with cirrhosis. Only about 50% respond with a sufficient reduction in their hepatic venous pressure gradient (HVPG) and NSBB may induce detrimental cardiac and renal effects in the presence of severe decompensation. We aimed to assess the effects of NSBB on haemodynamics using magnetic resonance imaging (MRI) and to assess if these haemodynamic changes were related to the disease severity and HVPG response. A prospective cross-over study of 39 patients with cirrhosis. Patients underwent hepatic vein catheterization and MRI with assessments of HVPG, cardiac function, systemic and splanchnic haemodynamics before and after propranolol infusion. Propranolol induced significant decreases in cardiac output (-12%) and blood flow of all vascular compartments, with the largest reductions seen in the azygos venous (-28%), portal venous (-21%), splenic (-19%) and superior mesenteric artery (-16%) blood flow. Renal artery blood flow fell by -5% in the total cohort, with a more pronounced reduction in patients without ascites than in those with ascites (-8% vs. -3%, p = .01). Twenty-four patients were NSBB responders. Their changes in HVPG after NSBB were not significantly associated with other haemodynamic changes. The changes in cardiac, systemic and splanchnic haemodynamics did not differ between NSBB responders and non-responders. The effects of acute NSBB blockade on renal flow seem to depend on the severity of the hyperdynamic state, with the largest reduction in renal blood flow in compensated patients compared to decompensated patients with cirrhosis. However, future studies are needed to assess the effects of NSBB on haemodynamics and renal blood flow in patients with diuretic-resistant ascites.

Invasive measurement of hepatic venous pressure gradient before resection of hepatocellular carcinoma.

To evaluate the role of hepatic venous pressure gradient (HVPG) measurement in patients with resectable hepatocellular carcinoma (HCC) we describe our experience with the procedure as part of our hospital standard preoperative algorithm. We present our protocol for this situation, the HVPG measurement procedure, and the results of our cohort. We performed a retrospective statistical analysis of all patients who underwent planned hepatic resection for HCC with HVPG measurement between 1/2016 and 1/2023. The cohort included 35 patients (30 males, mean age 69.5 years) who underwent HVPG measurement before liver resection for HCC. The success rate of measurement was 91.4%, with serious complications in 2.9% of cases. Due to the clinically significant portal hypertension (CSPH) 31.3% of patients were rejected for resection. Seventeen patients with excluded CSPH underwent resection with one case of a postoperative liver event, liver decompensation, representing 5.9% of them. One patient (5.9%) had a complicated postoperative course with fasciitis. None of the patients who underwent resection (88.2%) was readmitted to the hospital due to surgical complications or a liver event during 90 days of follow-up, and no death was reported. The median overall survival (OS) in the resected subgroup was 70 months (95% CI: 52-86), and in patients rejected for surgery (resection and transplantation) 35 months (95% CI: 13-48). HVPG measurement is the gold standard for the quantification of portal hypertension. Hepatic vein catheterization is invasive, but a safe procedure, with a clear impact on the management of resectable HCC.

CT-derived liver and spleen volume accurately diagnose clinically significant portal hypertension in patients with hepatocellular carcinoma

Clinically significant portal hypertension (CSPH) is a landmark in the natural history of cirrhosis, influencing clinical decisions in patients with hepatocellular carcinoma (HCC). Previous small series suggested that splanchnic volume measurements may predict portal hypertension. We aimed to evaluate whether volumetry obtained by standard multidetector computerised tomography (MDCT) can predict CSPH in patients with HCC. We included 175 patients with HCC, referred for hepatic venous pressure gradient (HVPG) evaluation, in whom contemporary MDCT was available. Liver volume, spleen volume (SV) and liver segmental volume ratio (LSVR: volume of the segments I-III/volume of the segments IV-VIII) were calculated semi-automatically from MDCT. Other non-invasive tests (NITs) were also employed. Volume parameters could be measured in almost 100% of cases with an excellent inter-observer agreement (intraclass correlation coefficient >0.950). SV and LSVR were independently associated with CSPH (HVPG ≥10mmHg) and did not interact with aetiology. The volume Index (VI), calculated as the product of SV and LSVR, predicted CSPH (AUC 0.83; 95% CI 0.77-0.89). Similar results were observed in an external cohort (n= 23) (AUC 0.87; 95% CI 0.69-1.00). Setting a sensitivity and specificity of 98%, VI could have avoided 35.9% of HVPG measurements. The accuracy of VI was similar to that of other NITs. VI also accurately predicted HVPG greater than 12, 14, 16 and 18mmHg (AUC 0.81 [95% CI 0.74-0.88], 0.84 [95% CI 0.77-0.91], 0.85 [95% CI 0.77-0.92] and 0.87 [95% CI 0.79-0.94], respectively). Quantification of liver and spleen volumes by MDCT is a simple, accurate and reliable method of CSPH estimation in patients with compensated cirrhosis and HCC. An increase in portal pressure strongly impacts outcomes after surgery in patients with early hepatocellular carcinoma (HCC). Direct measurement through hepatic vein catheterization remains the reference standard for portal pressure assessment, but its invasiveness limits its application. Therefore, we evaluated the ability of CT scan-based liver and spleen volume measurements to predict portal hypertension in patients with HCC. Our results indicate that the newly described index, based on quantification of liver and spleen volume, accurately predicts portal hypertension. These results suggest that a single imaging test may be used to diagnose and stage HCC, while providing an accurate estimation of portal hypertension, thus helping to stratify surgical risks.

Application of Ultrasound Elastography in Assessing Portal Hypertension.

Portal hypertension is a common manifestation in late-to-end-stage liver diseases and can cause severe complications such as ascites, hepatic encephalopathy, etc. However, an early diagnosis of portal hypertension is often difficult as it can be asymptomatic. Though the gold standard to diagnose portal hypertension is hepatic vein catheterization, ultrasound elastography is regarded as a noninvasive alternative that can be used to accurately predict portal hypertension and a few further complications such as gastro-esophageal varices. Since ultrasound elastography is available in most medical centers, and is cheaper and noninvasive, studying its function in predicting portal hypertension is of paramount importance. Therefore, this review generalized the results of recently published articles in order to establish the indicators that were related to diagnostic and prediction efficiency. Our study found that various technologies of ultrasound elastography could be used to predict portal hypertension with satisfactory diagnostic sensitivity, specificity, accuracy, and AUC. Meanwhile, we also recognized similar diagnostic efficiency of ultrasound elastography in gastro-esophageal varices.

Pulmonary vascular disease and exercise hemodynamics in chronic liver disease

Background & aimsPortopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are severe pulmonary vascular complications of chronic liver disease and strongly associated with morbidity and mortality. The prevalence of these complications is relatively high in patients evaluated for liver transplantation, however it is virtually unknown in patients with stable chronic liver disease. MethodsWe assessed the pulmonary hypertension (PH) and HPS prevalence in a prospective registry study of our liver out-patient clinic in a tertiary center. Between 2011 and 2016, consecutive patients with cirrhosis or non-cirrhotic portal hypertension were prospectively enrolled after written informed consent. We excluded patients with acute decompensation of liver disease and other causes of PH like severe chronic heart or lung diseases and chronic thromboembolic PH. HPS was diagnosed using contrast enhanced echocardiography and blood gas analysis. Patients were screened for PH using an algorithm implementing severity of dyspnea, echocardiography, cardiopulmonary exercise testing and exercise echocardiography employing a threshold of systolic pulmonary arterial pressure (SPAP) = 50 mmHg at peak exercise. If the algorithm indicated an increased PH risk, patients were invited for invasive investigations by means of right heart and hepatic vein catheter. We defined POPH as resting mPAP≥21 mmHg and PVR>3WU and PAWP<15 mmHg, mild PH as resting mPAP = 21–24 mmHg, and exercise PH as mPAP>30 mmHg and TPR >3 WU at peak exercise. ResultsTwo-hundred-five patients were enrolled (male 75%; cirrhosis 96%; median age 57 yrs). Sixty-seven patients (33%) fulfilled HPS criteria but only two (1.0%) for severe (PaO2:50–60 mmHg) or very severe HPS (PaO2<50 mmHg). In 18/77 patients (23%) undergoing exercise echocardiography, SPAP at peak exercise exceeded 50 mmHg. Finally, n = 3 (1.5%) patients were invasively diagnosed with POPH, n = 4 (2.9%) with mild PH and n = 2 with exercise PH. ConclusionIn chronic liver disease, excluding acute decompensation and other causes of PH, POPH and severe HPS are rare findings while mild to moderate HPS and mild PH or exercise PH are more frequent.

Systemic inflammation is linked to liver fibrogenesis in patients with advanced chronic liver disease.

Experimental evidence indicates that systemic inflammation (SI) promotes liver fibrogenesis. This study investigated the potential link between SI and fibrogenesis in patients with advanced chronic liver disease (ACLD). Serum biomarkers of SI (CRP, IL-6, procalcitonin [PCT]) and extracellular matrix (ECM) turnover (i.e., fibrogenesis/fibrolysis) were analysed in 215 prospectively recruited patients with ACLD (hepatic venous pressure gradient [HVPG] ≥6 mm Hg) undergoing hepatic vein catheterization. Patients with non-elective hospitalization or bacterial infection were excluded. Histological alpha-smooth muscle actin (α-SMA) area was quantified on full biopsy scans by automated morphometric quantification in a subset of 34 patients who underwent concomitant transjugular liver biopsy. Histological α-SMA proportionate area correlated with enhanced liver fibrosis (ELF) score (Spearman's ρ= 0.660, p< .001), markers of collagen formation (PRO-C3, ρ= 0.717, p< .001; PRO-C6, ρ= 0.526, p= .002) and tissue inhibitor of metalloproteinases-1 (TIMP1; ρ= 0.547, p< .001), indicating that these blood biomarkers are capable of reflecting the dynamic process of ECM turnover. CRP, IL-6 and PCT levels correlated with ELF, biomarkers of collagen synthesis/degradation and TIMP1, both in compensated and decompensated patients. Multivariate linear regression models (adjusted for HVPG) confirmed that CRP, IL-6 and PCT were independently linked to markers of liver fibrogenesis and ECM turnover. Systemic inflammation is linked to both liver fibrogenesis and ECM turnover in ACLD and this association is not confounded by the severity of liver disease, as evaluated by HVPG. Our study confirms experimental data on the detrimental impact of SI on ECM deposition and fibrosis progression in a thoroughly characterized cohort of patients with ACLD.

Binge drinking induces an acute burst of markers of hepatic fibrogenesis (PRO‐C3)

Binge drinking is associated with an increased risk of liver disease. Morbidity and mortality of alcohol-related liver disease (ALD) is associated with collagen deposition in the hepatic extracellular matrix (ECM). However, the acute effects of binge drinking on ECM turnover are unknown. We aimed to investigate the effects on hepatic ECM turnover following a binge drinking episode. We performed a pathophysiological intervention study with 15 non-alcoholic fatty liver disease (NAFLD) patients, 15 ALD patients and 10 healthy controls. We used 40% ethanol in 9mg/mL NaCl administered through a nasogastric tube to simulate binge drinking. Hepatic vein catheterisation allowed simultaneous hepatic- and systemic vein sampling. Markers of ECM formation and degradation were measured with competitive ELISA. The interstitial matrix formation marker PRO-C3 increased by 1.2ng/mL (10%, P<.001) 24hours after binge drinking. In participants with existing liver fibrosis determined by elevated baseline PRO-C3, hepatic levels increased by 0.09ng/mL (95% CI: 0.03-0.15, P=.005) while systemic PRO-C3 decreased 0.11ng/mL (95% CI: -0.15 to -0.06, P<.001) in 3hours. PRO-C8 increased by 30% (+0.9ng/mL, P=.014) in liver-diseased patients with F0-F1 but not in any other group. Twenty-four-hour changes in systemic C3M and PRO-C3 were not associated (P=.911). Binge drinking induced an acute burst of PRO-C3 in healthy individuals and patients with liver disease. Markers of ECM degradation were not correlated to markers of ECM formation, suggesting that even a single episode of binge drinking promotes excessive hepatic fibrogenesis.

Decompensation in Advanced Nonalcoholic Fatty Liver Disease May Occur at Lower Hepatic Venous Pressure Gradient Levels Than in Patients With Viral Disease

Portal hypertension is the strongest predictor of hepatic decompensation and death in patients with cirrhosis. However, its discriminatory accuracy in patients with nonalcoholic fatty liver disease (NAFLD) has been challenged because hepatic vein catheterization may not reflect the real portal vein pressure as accurately as in patients with other etiologies. We aimed to evaluate the relationship between hepatic venous pressure gradient (HVPG) and presence of portal hypertension-related decompensation in patients with advanced NAFLD (aNAFLD). Multicenter cross-sectional study included 548 patients with aNAFLD and 444 with advanced RNA-positive hepatitis C (aHCV) who had detailed portal hypertension evaluation (HVPG measurement, gastroscopy, and abdominal imaging). We examined the relationship between etiology, HVPG, and decompensation by logistic regression models. We also compared the proportions of compensated/decompensated patients at different HVPG levels. Both cohorts, aNAFLD and aHVC, had similar baseline age, gender, Child-Pugh score, and Model for End-Stage Liver Disease score. Median HVPG was lower in the aNAFLD cohort (13 vs 15 mmHg) despite similar liver function and higher rates of decompensation in aNAFLD group (32% vs 25%; P= .019) than in the aHCV group. For any of the HVPG cutoff analyzed (&lt;10, 10-12, or 12 mmHg) the prevalence of decompensation was higher in the aNAFLD group than in the aHCV group. Patients with aNAFLD have higher prevalence of portal hypertension-related decompensation at any value of HVPG as compared with aHCV patients. Longitudinal studies aiming to identify HVPG thresholds able to predict decompensation and long-term outcomes in aNAFLD population are strongly needed.

Nonselective Beta-Blockers in Compensated Cirrhosis: Preventing Variceal Hemorrhage or Preventing Decompensation?

Nonselective Beta-Blockers in Compensated Cirrhosis: Preventing Variceal Hemorrhage or Preventing Decompensation?

The Psychometric Hepatic Encephalopathy Syndrome score does not correlate with blood ammonia, endotoxins or markers of inflammation in patients with cirrhosis.

The pathogenesis of hepatic encephalopathy (HE) remains unclear but impaired clearance of gut-derived neurotoxins and increased systemic inflammation are thought to play key roles. The diagnosis is based on detection of neurophysiological and neuropsychometric abnormalities. The Psychometric Hepatic Encephalopathy Score (PHES) have been found to correlate with markers of systematic inflammation including interleukin 6, C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α). This study explores the associations between the PHES score and systemic inflammation, endotoxins and disease severity using baseline data from a trial involving patients with cirrhosis and minimal or no HE (NCT01769040). Arterial blood was obtained during hepatic vein catheterization, from 54 patients [median age 55 (range, 33-70) years; 83% men] with decompensated but stable cirrhosis. None had clinical evidence of HE but 34 (55.6%) had an abnormal PHES score indicating the presence of minimal HE. Relationships were sought between the PHES score and markers of systemic inflammation, high sensitivity-CRP, cytokines (SDF-1α, TGF-b1, IP-10, IL-6, 10 and 18, and TNF-α; lipopolysaccharide (LPS), the lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14); and the blood ammonia. No significant relationships were found between the PHES score and any of the variables tested with the single exception of the correlation with serum IL-6 (r=-0.29, 95% confidence interval, -0.53 to -0.02, P=0.031). No independent predictors of the PHES score were identified in regression analyses. No predictive associations were identified between the PHES scores and circulating blood ammonia, endotoxins, or markers of systemic inflammation in this patient population.

THE ROLE OF INVASIVE AND NON-INVASIVE MEASUREMENTS OF HVPG IN DECISION MAKING IN PATIENTS WITH PORTAL HYPERTENSION AND ESOPHAGEAL VARICES

Many researchers and clinicians have taken the value of hepatic venous pressure gradient (HVPG) as an essential prognostic factor in subjects with chronic liver disorders. And HVPG alterations characterize a predictive value in subjects at the beginning of the disease (HVPG 6 – 10 mmHg) as well as in subjects in whom hemodynamically significant portal hypertension has developed (HVPG ≥ 10 mmHg). Our review aims to present the feasibility and applicability of HVPG in modern clinical practice in patients with liver cirrhosis, including invasive and non-invasive methods. HVPG measurement is a feasible method with a favorable safety profile. However, hemodynamically significant portal hypertension also might be determined using non-invasive options as elastography, magnetic resonance imaging, and indices derived from laboratory parameters, e.g., aspartate aminotransferase-to-platelet ratio, platelet count/spleen diameter ratio, or VITRO score. Hepatic vein catheterization with the evaluation of HVPG is the current gold standard for determining portal pressure; however, new non-invasive techniques are nowadays more frequently used.

Outcomes of transjugular liver biopsies for liver transplant recipients with bicaval and piggyback hepatic vein anastomoses.

Liver transplant hepatic venous anastomoses are usually created using "bicaval" or "piggyback" techniques, which may result in unfavorable angulation between the inferior vena cava and hepatic veins, and makes hepatic vein catheterization and tissue sampling during transjugular liver biopsy (TLB) technically challenging. To compare the technical successes and complications of TLBs for recipients of liver transplants with bicaval and piggyback hepatic vein anastomoses. Information on type of hepatic vein surgical anastomosis was available for 190 adult patients in whom 306 consecutive TLBs were performed during 2009-2017: 158 with bicaval and 148 with piggyback anastomoses. The primary outcome of procedural success was defined as obtaining a tissue sample sufficient to make a pathologic diagnosis. A technical success rate of 97% with adequate liver tissue for diagnosis was similar between the anastomotic groups (P = 0.50). TLB was unsuccessful in 3% of patients with piggyback anastomoses due to unfavorable hepatic venous anatomy whereas biopsy was successful in all patients with bicaval anastomoses (P = 0.02). Fluoroscopy times were not significantly different (12.1 vs. 13.9 min, P = 0.08). Rates of major complication were similar between the two groups (3% vs. 3%, P > 0.99). TLB is safe and effective for liver transplant patients regardless of the type of hepatic vein anastomosis. While failure to catheterize or advance the stiffened biopsy cannula into the hepatic vein is more likely to occur in patients with piggyback anastomoses, this is a rare occurrence.

Prevalence and characteristics of portopulmonary hypertension in cirrhotic patients who underwent both hepatic vein and pulmonary artery catheterization

The subjects were 335 patients with portal hypertension diagnosed by hepatic vein pressure gradient (HVPG). Among them, 186 patients received measurements of pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR). PoPH was diagnosed by PAP >20mmHg, PVR ≥3 Wood units (WU) and PAWP ≤15mmHg. The Child-Pugh classification was class A in 53, B in 92 and C in 41 patients. Median (range) values of HVPG, PAP, PVR and PAWP were 18.4 (5.5-39.0) mmHg, 12.9 (6.6-40.8) mmHg, 0.8 (0.1-4.5) WU and 7.5 (2.2-15.4) mmHg, respectively. Of six patients with PAP >20mmHg, four had autoimmune hepatitis or primary biliary cholangitis, with the prevalence being significantly higher than that in patients with PAP ≤20mmHg. Meanwhile, no significant difference was noted in the hepatic functional reserve or HVPG between patients with PAP >20mmHg and ≤20mmHg. Only two patients met the diagnostic criteria of PoPH and both patients were Child-Pugh B. The Child-Pugh score and HVPG were not associated with PoPH. Our study demonstrated that only two patients were complicated by PoPH. High PAP values were noted in patients with primary biliary cholangitis or autoimmune hepatitis. However, the presence of PoPH and high PAP were not associated with the degree of hepatic functional reserve or HVPG.

1902-P: Insulin Pulses Do Not Inhibit Glucagon Secretion in Nondiabetic Humans

Type 2 diabetes (T2DM) is characterized by defects in insulin secretion and glucagon suppression. It has been assumed that defective glucagon secretion arises due to impaired insulin secretion. Indeed, prior work suggests that pulsatile insulin secretion has an inverse relationship with post-prandial glucagon secretion. However, more recent data suggest that dysregulation of glucagon secretion in prediabetes occurs early, and independently, of changes in insulin secretion. During a series of experiments examining the mechanisms underlying prediabetes, we studied 29 nondiabetic subjects (age = 44 ± 2, BMI 28 ± 1 Kg/m2). Hepatic vein catheterization allowed sampling of insulin and glucagon at 2 minute intervals during fasting and during a hyperglycemic clamp (150mg/dL). Mean insulin concentrations rose from fasting (33 ± 1 vs. 144 ± 2 pmol/L, p&amp;lt;0.01) while glucagon was suppressed (96 ± 1 vs. 62 ± 1 ng/L, p&amp;lt;0.01) during the clamp. A cross-correlation analysis of the two hormones showed, on average, a small in-phase coordination between insulin and glucagon pulses during fasting, which inverted during hyperglycemia (0.2 ± 0.1 vs. -0.4 ± 0.1, p&amp;lt;0.01). Subsequently, Cross-Approximate Entropy (Cross-ApEn), a technique for comparing synchronicity between two time series, was used to evaluate their interaction. This showed a moderate level of synchronicity, unaffected by glucose concentrations, whether calculated using glucagon as the template to assess pattern reproducibility in insulin concentration (0.78 ± 0.03 vs. 0.76 ± 0.03, fasting vs. hyperglycemia), or when using insulin as the template for the glucagon pattern (0.78 ± 0.02 vs. 0.76 ± 0.03, fasting vs. hyperglycemia). The values of Cross-ApEn did not differ between the two scenarios, suggesting the interaction between the two hormones is not driven by either. Overall these data suggest that, on a minute-to-minute basis, direct control and secretion of glucagon is not mediated (or restrained) by insulin. Disclosure M.C. Laurenti: None. C. Dalla Man: Research Support; Self; Sanofi-Aventis Deutschland GmbH. R.T. Varghese: None. R.A. Rizza: None. A. Matveyenko: None. C. Cobelli: None. A. Vella: Advisory Panel; Self; vTv Therapeutics, Zealand Pharma A/S. Research Support; Self; Novo Nordisk A/S, Xeris Pharmaceuticals, Inc. Funding National Institutes of Health (DK78646, DK116231)

Transjugular intrahepatic portosystemic shunt placement: portal vein puncture guided by 3D/2D image registration of contrast-enhanced multi-detector computed tomography and fluoroscopy

BackgroundTo assess the technical feasibility, success rate, puncture complications and procedural characteristics of transjugular intrahepatic portosystemic shunt (TIPS) placement using a three-dimensional vascular map (3D-VM) overlay based on image registration of pre-procedural contrast-enhanced (CE) multi-detector computed tomography (MDCT) for portal vein puncture guidance.Materials and methodsOverall, 27 consecutive patients (59 ± 9 years, 18male) with portal hypertension undergoing elective TIPS procedure were included. TIPS was guided by CE-MDCT overlay after image registration based on fluoroscopic images. A 3D-VM of the hepatic veins and the portal vein was created based on the pre-procedural CE-MDCT and superimposed on fluoroscopy in real-time. Procedural characteristics as well as hepatic vein catheterization time (HVCT), puncture time (PT), overall procedural time (OPT), fluoroscopy time (FT) and the dose area product (DAP) were evaluated. Thereafter, HVCT, PT, OPT and FT using 3D-VM (61 ± 9 years, 14male) were compared to a previous using classical fluoroscopic guidance (53 ± 9 years, 21male) for two interventional radiologist with less than 3 years of experience in TIPS placement.ResultsAll TIPS procedure using of 3D/2D image registered 3D-VM were successful with a significant reduction of the PSG (p < 0.0001). No clinical significant complication occurred. HVCT was 14 ± 11 min, PT was 14 ± 6 min, OPT was 64 ± 29 min, FT was 21 ± 12 min and DAP was 107.48 ± 93.84 Gy cm2. HVCT, OPT and FT of the interventionalist with less TIPS experience using 3D/2D image registered 3D-VM were statistically different to an interventionalist with similar experience using fluoroscopic guidance (pHVCT = 0.0022; pOPT = 0.0097; pFT = 0.0009). PT between these interventionalists was not significantly different (pPT = 0.2905).ConclusionTIPS placement applying registration-based CE-MDCT vessel information for puncture guidance is feasible and safe. It has the potential to improve hepatic vein catherization, portal vein puncture and radiation exposure.

Effect of curcumin-lipiodol emulsion combined with absorbable anti-adhesion film through double embolic pathway on angiogenesis and overall survival (OS) time of VX2 liver cancer rabbits

BackgroundCurcumin is a promising anti-tumor drug in recent years. The main function of absorbable anti-adhesion film is to prevent adhesions after surgical operation. The effects of curcumin-lipiodol emulsion injected via the hepatic artery and portal vein catheter combined with using absorbable anti-adhesion film around the liver angiogenesis are unknown. This article mainly discusses the effects of these combined strategies on the inhibition or reduction of postoperative angiogenesis and prolonging survival time of rabbit model.MethodsForty model rabbits with VX2 liver cancer were divided into four groups. Group A is the control group and its intervention is a simple lipiodol emulsion group. The intervention in group B was a simple lipiodol emulsion combined with an anti-adhesion membrane. The intervention in group C was a mixture of curcumin and lipiodol. The intervention in group D was a mixed emulsion of curcumin and lipiodol combined with an anti-adhesion membrane. The levels of aspartate aminotransferase (ALT) and alanine aminotransferase (AST) in the model rabbits were compared to analyze the damage of liver cells 1 day before embolization and 3, 7, 14 days after the embolization. In addition, the levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in residual cancer tissues were determined by immunohistochemistry and Western blot. Finally, overall survival time (OS) of each group was recorded.ResultsThe results showed that the ALT and AST levels of venous blood before and after embolization in each group of rabbits were not changed significantly (P>0.05). The levels of VEGF and MVD in the group C and group D were lower than those in the group A (P<0.05). However, there was no significant difference between group B and group A (P>0.05). The decrease of VEGF and MVD in group D was most obvious, and group D had a significant difference compared with group C (P<0.05). Western blot analysis showed that the protein expression of VEGF was consistent with immunohistochemical staining. The overall survival (OS) time of group B showed no significant difference compared with group A (P>0.05). The OS time of group C and group D was longer than that of group A (P<0.05). Group D showed significantly difference on prolongation of the survival time than group C (P<0.05).ConclusionsOverall, the curcumin-lipiodol emulsion injected into the portal vein and hepatic artery supplying the tumor can significantly inhibit angiogenesis and play a role in prolonging the OS time of model rabbits. The application of anti-adhesion film alone cannot inhibit tumor angiogenesis and play a role in prolonging the OS time of model rabbits. However, curcumin-lipiodol emulsion combined with anti-adhesion film can obviously promote these effects.