Restrictive Pulmonary Dysfunction May Increase Blood Loss During Liver Resection.

BACKGROUND: Restrictive pulmonary dysfunction (RPD) is a risk factor for perioperative complications during gastrointestinal surgery. We hypothesized that high airway pressure due to RPD results in increased intraoperative blood loss during liver surgery. Thus, we investigated the effects of RPD on perioperative outcomes for liver resection. METHODS: This study included 496 patients who underwent curative liver resection at our hospital between April 2009 and April 2020. Perioperative outcomes for the RPD and control groups were compared. Restrictive pulmonary dysfunction was defined as % vital capacity <80%. RESULTS: Forty-one patients (8.3%) had RPD. No significant differences were observed in intraoperative blood losses (440 mL vs 320 mL, P = .340), overall complication rates (29.3% vs 31.2%, P = .797), or pulmonary complication rates (4.9% vs 9.0%, P = .286) between the RPD and control groups. In the 256 patients who underwent anatomical liver resection, 18 patients (7.0%) had RPD. The intraoperative blood loss was significantly higher in the RPD group (925 mL vs 456 mL, P = .013), but no differences in the overall complication rates (44.4% vs 37.3%, P = .528) or pulmonary complication rates (11.1% vs 10.5%, P = .589) between the two groups were detected. A multivariate analysis showed that RPD was an independent risk factor for intraoperative blood loss ≥500 mL during anatomical liver resection (odds ratio 4.132; 95% confidence interval 1.135-15.045; P = .031). DISCUSSION: Restrictive pulmonary dysfunction may be a risk factor for intraoperative blood loss during anatomical liver resection, which requires exposure of the main hepatic vein.

Test-Retest Reliability and Consistency of HVPG and Impact on Trial Design: A Study in 289 Patients from 20 Randomized Controlled Trials.

BACKGROUND AND AIMS: Portal hypertension (PH) is a major driver for cirrhosis complications. Portal pressure is estimated in practice by the HVPG. The assessment of HVPG changes has been used for drug development in PH. This study aimed at quantifying the test-retest reliability and consistency of HVPG in the specific context of randomized controlled trials (RCTs) for the treatment of PH in cirrhosis and its impact on power calculations for trial design. APPROACH AND RESULTS: We conducted a search of published RCTs in patients with cirrhosis reporting individual patient-level data of HVPG at baseline and after an intervention, which included a placebo or an untreated control arm. Baseline and follow-up HVPGs in the control groups were extracted after digitizing the plots. We assessed reliability and consistency and the potential impact of study characteristics. We retrieved a total of 289 before and after HVPG measurements in the placebo/untreated groups from 20 RCTs. The time span between the two HVPG measurements ranged between 20 minutes and 730 days. Pre-/post-HVPG variability was lower in studies including only compensated patients; therefore, modeled sample size calculations for trials in compensated cirrhosis were lower than for decompensated cirrhosis. A higher proportion of alcohol-associated cirrhosis and unicentric trials was associated with lower differences between baseline and follow-up measurements. The smallest detectable difference in an individual was 26% and 30% in compensated and decompensated patients, respectively. CONCLUSIONS: The test-retest reliability of HVPG is overall excellent. Within-individual variance was higher in studies including higher proportions of decompensated patients. These findings should be taken into account when performing power analysis for trials based on the effects on HVPG or when considering HVPG as a tool to guide therapy of PH.

Patterns of acute decompensation in hospitalized patients with cirrhosis and course of acute-on-chronic liver failure.

INTRODUCTION: Recently, based on data from the PREDICT study, the European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium proposed pathophysiological/prognostic groups in hospitalized patients with cirrhosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre-acute-on-chronic liver failure (pre-ACLF), and ACLF. We evaluated the outcomes of these subgroups in a real-life cohort of hospitalized patients with cirrhosis. METHODS: Patients with cirrhosis developing first AD between 09/2010 and 12/2017 at the Vienna General Hospital were evaluated for this retrospective analysis. RESULTS: Two hundred and ten patients with cirrhosis (aged 57.6 ± 11.8 years) including n = 45 (21.4%) SDC, n = 100 (47.6%) UDC, n = 28 (13.3%) pre-ACLF, and n = 37 (17.6%) with ACLF were considered. The proposed AD subgroups discriminated between patients with favorable (1-year mortality: SDC: 6.7% and UDC: 19.6%) and dismal prognosis (90-day mortality: pre-ACLF: 42.9%). Interestingly, systemic inflammation gradually increased (e.g., C-reactive protein, SDC: 0.9 mg/dl, vs. UDC: 2.0 mg/dl vs. pre-ACLF: 3.2 mg/dl, p < 0.001) while renal function was progressively deteriorating (creatinine levels, SDC: 0.8 mg/dl vs. UDC: 0.9 mg/dl vs. pre-ACLF: 1.2 mg/dl, p < 0.001) across prognostic subgroups in patients with cirrhosis. DISCUSSION: The recently proposed pathophysiological/prognostic EF-CLIF subgroups are also reproduceable in a real-life cohort of cirrhotic patients. As ACLF is a common and important complication, patients at risk of pre-ACLF at index AD should be evaluated and if disease proceeds, been treated early and aggressively to avoid excessive mortality.

Identification of the Most Important Subset of Doppler, Laboratory, and Clinical Parameters for Serial TIPS Evaluation.

OBJECTIVE. The purpose of the present study was to identify the subset of a wide range of serial Doppler, laboratory, and clinical parameters most predictive (both individually and in combination) of TIPS dysfunction in a large patient sample. MATERIALS AND METHODS. The medical records of 189 patients who had undergone TIPS procedures were analyzed. The patients (mean age, 52 years; 62% of whom were men) had undergone 1139 Doppler studies and 323 portovenograms. Laboratory parameters included model for end-stage liver disease (MELD) scores, serum albumin levels, presence of ascites, and time since last intervention. Doppler parameters included intrashunt velocities, temporal change in intrashunt velocities, main portal vein velocity, direction of flow in the left portal hepatic vein, and venous pulsatility index. Statistical analysis used ROC, univariate, and multivariate regression models to assess the parameters both individually and in combination. Shunt dysfunction was defined by a portosystemic gradient of more than 12 mm Hg. RESULTS. The laboratory and clinical parameters of greatest predictive value included the MELD score and the time since the last intervention. The Doppler parameters that were of greatest predictive value included the change in velocity at the hepatic venous end and the left portal vein flow direction. Multivariate models produced an AUC of 0.74. Differences between functional and dysfunctional shunts were also statistically significant for absolute velocity at the hepatic venous end, the change in velocity within the stent, and the temporal change in the mid shunt velocity. CONCLUSION. The subset of serial parameters most predictive of TIPS dysfunction are the temporal change in the velocity at the hepatic venous end, the absolute velocity at the hepatic venous end, the direction of flow in the left portal venous branch, and changes in the MELD score.

Second-harmonic generation (SHG) microscopy and hepatic venous pressure gradient-based validation of a novel histological staging system for alcoholic hepatitis.

Alcoholic hepatitis (AH) lacks specific histological staging. A novel fibrosis staging that encompasses perisinusoidal fibrosis and cirrhosis sub-stages, substantiated by Hepatic venous pressure gradient (HVPG) and automated fibrosis quantification, is imperative. To correlate novel histological staging system of AH with second-harmonic generation microscopy (SHG)-based q-fibrosis, HVPG, and activated hepatic stellate cells (HSCs). Liver biopsies of AH (n = 175) were staged semi-quantitatively as F0, F1, F2, F3A and F3B and Laennec substages of cirrhosis 4A, 4B and 4C. Stages were correlated with SHG q-fibrosis parameters, HVPG and HSCs. Mean age 41.2 ± 9.4 years, 96.6% males, bilirubin 20.58 ± 8.0 mg/dl and Maddrey's discriminant function 78.9 ± 36.7 displayed advanced fibrosis in 98.6%. With increasing histological stages, an increase in q-fibrosis indices and mean HVPG (p < 0.0001) were recorded; stage 4C showed the most significant difference from other stages (p < 0.000). Stages 3A and 3B were comparable with the stages 4A and 4B, respectively, for q-fibrosis (p = 1) and HVPG (p = 1). HSCs (> 30%) were significantly higher in stage 3 (75%) compared with 4 (49%) and 2 (59%), p = 0.018. Overall agreement for histological staging was excellent for all stages (0.82). SHG quantified fibrosis and HVPG corroborates the novel histological staging of AH. Expansive PCF matches with collagen content and clinical severity to early sub-stages of cirrhosis. This highlights the need for an accurate quantification and inclusion of PCF as a separate stage. SHG-based quantification can be a useful adjunct to histological fibrosis staging systems.

Agreement between wedged hepatic venous pressure and portal pressure in non-alcoholic steatohepatitis-related cirrhosis.

BACKGROUND & AIMS: Wedge hepatic vein pressure (WHVP) accurately estimates portal pressure (PP) in alcohol- or viral hepatitis-related cirrhosis. Whether this also holds true in cirrhosis caused by non-alcoholic steatohepatitis (NASH) is unknown. We aimed to evaluate the agreement between WHVP and PP in patients with NASH cirrhosis in comparison to patients with alcohol- or HCV-related cirrhosis. METHODS: All consecutive patients with NASH cirrhosis treated with a transjugular intrahepatic portosystemic shunt (TIPS) in 3 European centres were included (NASH group; n = 40) and matched with 2 controls (1 with alcohol-related and 1 with HCV-related cirrhosis) treated with TIPS contemporaneously (control group; n = 80). Agreement was assessed by Pearson's correlation (R), intra-class correlation coefficient (ICC), and Bland-Altman method. Disagreement between WHVP and PP occurred when both pressures differed by >10% of PP value. A binary logistic regression analysis was performed to identify factors associated with this disagreement. RESULTS: Correlation between WHVP and PP was excellent in the control group (R 0.92; p <0.001; ICC 0.96; p <0.001) and moderate in the NASH group (R 0.61; p <0.001; ICC 0.74; p <0.001). Disagreement between WHVP and PP was more frequent in the NASH group (37.5% vs. 14%; p = 0.003) and was mainly because of PP underestimation. In uni- and multivariate analyses, only NASH aetiology was associated with disagreement between WHVP and PP (odds ratio 4.03; 95% CI 1.60-10.15; p = 0.003). CONCLUSIONS: In patients with decompensated NASH cirrhosis, WHVP does not estimate PP as accurately as in patients with alcohol- or HCV-related cirrhosis, mainly because of PP underestimation. Further studies aimed to assess this agreement in patients with compensated NASH cirrhosis are needed. LAY SUMMARY: Portal pressure is usually assessed by measuring wedge hepatic vein pressure because of solid evidence demonstrating their excellent agreement in alcohol- and viral hepatitis-related cirrhosis. Our results show that in patients with decompensated cirrhosis caused by non-alcoholic steatohepatitis, wedge hepatic vein pressure estimates portal pressure with less accuracy than in patients with other aetiologies of cirrhosis, mainly because of portal pressure underestimation.

Parietal Peritoneum as a Novel Substitute for Middle Hepatic Vein Reconstruction During Living Donor Liver Transplantation.

BACKGROUND: Although autologous, cryopreserved, or artificial vascular grafts can be used as interpositional vascular substitutes for middle hepatic vein (MHV) reconstruction during living donor liver transplantation (LDLT), they are not always available, are limited in size and length, and are associated with risks of infection. This study aimed to evaluate the parietal peritoneum as a novel substitute for MHV reconstruction during LDLT. METHODS: Prospectively collected data of 15 patients who underwent LDLT using the right liver with reconstruction of MHV using the recipients' own parietal peritoneum graft were retrospectively reviewed. RESULTS: The 1-, 2-, 3-, and 5-mo patency rates were 57.1%, 57.1%, 57.1%, and 28.6%, respectively. Among the 15 cases assessed, the most recent 6 cases showed patent graft flow until discharge with 1-, 2-, 3-, and 5-mo patency rates of 80.0%, 80.0%, 80.0%, and 20.0%, respectively. All patients survived with tolerable liver function tests. There were no significant congestion-related problems, except for 1 patient who experienced MHV thrombosis requiring aspiration thrombectomy and stent insertion. There were no infection-related complications. All patients survived to the final follow-up, with a minimum follow-up duration of 8 mo. When comparing the latter 6 cases of peritoneal grafts and the recent 28 cases of conventional polytetrafluorethylene graft, the overall patency rate of the polytetrafluorethylene group was higher (P = 0.002). There were no major differences other than long-term patency rate. CONCLUSIONS: Parietal peritoneum may be a novel autologous substitute for MHV reconstruction during LDLT.

Application of Hepatic Transit Time and Shear Wave Velocity in Assessing Portal Pressure in Patients with Cirrhotic Portal Hypertension.

The aim of the study described here was to explore the value of hepatic transit time (HTT) and shear wave velocity (SWV) in diagnosing cirrhotic portal hypertension. Fifty-seven patients had undergone esophagogastric varicose vein embolization (group OBS) and 50 healthy controls (group CON) were retrospectively compared with respect to HTT (arterial-hepatic vein [HA-HVTT], portal vein-hepatic vein [PV-HVTT], liver parenchyma-hepatic vein [PA-HVTT]) and SWV to analyze their efficacy in diagnosing cirrhotic portal hypertension. The correlations between SWV/HTT and free portal pressure (FPP) in group OBS were also analyzed. Compared with group CON, group OBS had a shorter HTT and faster SWV. The area under the curve (AUC) of PV-HVTT (0.93) was higher than those of HA-HVTT (0.75) and PA-HVTT (0.64), the AUCs of PV-HVTT (0.93, threshold 7.9 s) and SWV (0.91, threshold 2.0 cm/s) did not statistically differ (z = 0.35, p = 0.73). HTT and FPP in group OBS had a negative correlation. In conclusion, HTT and SWV can be used to diagnose cirrhotic portal hypertension without difference in diagnostic efficacy, and HTT is more meaningful for assessing the changes in portal pressure.

Novel imaging-based approaches for predicting the hepatic venous pressure gradient in a porcine model of liver cirrhosis and portal hypertension.

AIMS: Hepatic venous pressure gradient (HVPG) is critical for staging and prognosis prediction of portal hypertension (PH). However, HVPG measurement has limitations (e.g., invasiveness). This study examined the value of non-invasive, imaging-based approaches including magnetic resonance elastography (MRE) and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for the prediction of HVPG in a porcine model of liver cirrhosis and PH. MAIN METHODS: Male Bama miniature pigs were used to establish a porcine model of liver cirrhosis and PH induced by embolization. They were randomly assigned to an experimental group (n = 12) and control group (n = 3). HVPG was examined before and after transjugular intrahepatic portosystemic shunt (TIPS). MRE and IVIM-DWI were performed to obtain quantitative parameters including liver stiffness (LS) in MRE, tissue diffusivity (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) in IVIM-DWI. The correlation between HVPG and the parameters was assessed. KEY FINDINGS: LS values were significantly greater in the experimental group, while f values were significantly decreased at 4, 8, and 12 weeks after embolization compared to the control group. Furthermore, HVPG was significantly lower immediately after versus before TIPS. In parallel, LS and f values showed significant alterations after TIPS, and these changes were consistent with a reduction in HVPG. Spearman analysis revealed a significant correlation between the parameters (LS and f) and HVPG. The equation was eventually generated for prediction of HVPG. SIGNIFICANCE: The findings show a good correlation between HVPG and the quantitative parameters; thus, imaging-based techniques have potential as non-invasive methods for predicting HVPG.

Impact of Intrahepatic Venovenous Shunt on Hepatic Venous Pressure Gradient Measurement.

PURPOSE: To quantitatively analyze the impact of intrahepatic venovenous shunt (IHVS) on hepatic venous pressure gradient (HVPG) measurement. MATERIALS AND METHODS: From 2015 to 2019, 222 HVPG measurements performed during transjugular intrahepatic portosystemic shunt creation were eligible for this study. Digital subtraction angiography (DSA) software color-coded each pixel of a two-dimensional DSA series by time-intensity curve to classify IHVS. Different degrees of IHVS were found in 36.5% of patients (81/222). Mild IHVS was found in 10.8% of patients (24/222), moderate IHVS was found in 10.8% of patients (24/222), and severe IVHS was found in 14.9% of patients (33/222). RESULTS: Mean wedged hepatic vein pressure (WHVP) and HVPG were significantly lower in patients with IHVS compared with patients without IHVS (WHVP: 17.78 mm Hg ± 7.00 vs 24.89 mm Hg ± 8.69, P = .001; HVPG: 11.93 mm Hg ± 5.76 vs 18.6 mm Hg ± 6.85, P < .001). Mild IHVS had little effect on WHVP and HVPG. Mean WHVP and HVPG were 11 mm Hg lower in patients with moderate IHVS (WHVP: 20.38 mm Hg ± 8.38 vs 31.5 mm Hg ± 9.39, P = .026; HVPG: 13.88 mm Hg ± 6.33 vs 25.00 mm Hg ± 9.81, P < .001) and 15 mm Hg lower in patients with severe IHVS (WHVP: 13.45 mm Hg ± 5.28 vs 28.64 mm Hg ± 6.38, P = .017; HVPG: 8.27 mm Hg ± 3.85 vs 23.45 mm Hg ± 6.95, P < .001) than mean portal vein pressure and portal vein gradient. CONCLUSIONS: For patients with moderate or severe IHVS, HVPG might greatly underestimate the actual value of portal vein pressure, and the portal vein should be catheterized to measure portal pressure.

The use of venous Doppler to predict adverse kidney events in a general ICU cohort.

BACKGROUND: Changes in Doppler flow patterns of hepatic veins (HV), portal vein (PV) and intra-renal veins (RV) reflect right atrial pressure and venous congestion; the feasibility of obtaining these assessments and the clinical relevance of the findings is unknown in a general ICU population. This study compares the morphology of HV, PV and RV waveform abnormalities in prediction of major adverse kidney events at 30 days (MAKE30) in critically ill patients. STUDY DESIGN AND METHODS: We conducted a prospective observational study enrolling adult patients within 24 h of admission to the ICU. Patients underwent an ultrasound evaluation of the HV, PV and RV. We compared the rate of MAKE-30 events in patients with and without venous flow abnormalities in the hepatic, portal and intra-renal veins. The HV was considered abnormal if S to D wave reversal was present. The PV was considered abnormal if the portal pulsatility index (PPI) was greater than 30%. We also examined PPI as a continuous variable to assess whether small changes in portal vein flow was a clinically important marker of venous congestion. RESULTS: From January 2019 to June 2019, we enrolled 114 patients. HV abnormalities demonstrate an odds ratio of 4.0 (95% CI 1.4-11.2). PV as a dichotomous outcome is associated with an increased odds ratio of MAKE-30 but fails to reach statistical significance (OR 2.3 95% CI 0.87-5.96), but when examined as a continuous variable it demonstrates an odds ratio of 1.03 (95% CI 1.00-1.06). RV Doppler flow abnormalities are not associated with an increase in the rate of MAKE-30 INTERPRETATION: Obtaining hepatic, portal and renal venous Doppler assessments in critically ill ICU patients are feasible. Abnormalities in hepatic and portal venous Doppler are associated with an increase in MAKE-30. Further research is needed to determine if venous Doppler assessments can be useful measures in assessing right-sided venous congestion in critically ill patients.

Measurement of the Hepatic Venous Pressure Gradient and Transjugular Liver Biopsy.

Here we provide a detailed protocol describing the clinical procedure of hepatic venous pressure gradient (HVPG) measurement in patients with advanced chronic liver disease followed by an instruction for transjugular biopsy. Under local anesthesia and ultrasound guidance, a catheter introducer sheath is placed in the right internal jugular vein. Using fluoroscopic guidance, a balloon catheter is advanced into the inferior vena cava (IVC) and inserted into a large hepatic vein. Correct and sufficient wedge position of the catheter is ensured by injecting contrast media while the balloon is blocking the outflow of the cannulated hepatic vein. After calibrating the external pressure transducer, continuous pressure recordings are obtained with triplicate recordings of the wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP). The difference between FHVP and WHVP is referred to as HVPG, with values ≥10 mm Hg indicating clinically significant portal hypertension (CSPH). Before removing the catheter, pressure readings obtained in the IVC at the same level, as well as the right atrial pressure are recorded. Finally, a transjugular liver biopsy can be obtained via the same vascular route. Different systems are available; however, core biopsy needles are preferred over aspiration needles, especially for cirrhotic livers. Again, under fluoroscopic guidance a biopsy needle introducer sheath is advanced into an hepatic vein. Next, the transjugular biopsy needle is gently advanced through the introducer sheath: (i) in case of aspiration biopsy, the needle is advanced into the liver parenchyma under aspiration and then removed quickly, or (ii) in case of a core biopsy, the cutting-mechanism is triggered inside the parenchyma. Several separate passages can be safely performed to obtain sufficient liver specimens via transjugular biopsy. In experienced hands, the combination of these procedures takes about 30-45 min.

Feasibility and safety of bisegmentectomy 7-8 while preserving hepatic venous outflow of the right liver - A retrospective cohort study.

BACKGROUND: When a hepatic tumor is deeply located in segments 7 and 8 around the right hepatic vein (RHV), right hemihepatectomy (RH) could be excessive owing to the resection of large tumor-free segments. This study aimed to evaluate the feasibility and safety of bisegmentectomy 7-8 (S7-8) and to compare its surgical outcomes with those of RH. MATERIALS AND METHODS: Consecutive patients who underwent S7-8 and RH were enrolled in this study. In the S7-8 group, 14 patients with an obvious inferior right hepatic vein (IRHV) (median: 6 mm; range: 3.6-8.8 mm) underwent S7-8 without hepatic vein reconstruction. RHV reconstruction was performed in six patients without an IRHV, involving direct anastomosis of the RHV in five patients and reconstruction using a cryo-preserved iliac vein in one patient. RESULTS: A total of 61 patients were included (20 in S7-8 group; 41 in RH group). No significant differences were observed other than higher a model of end-stage liver disease score in the RH group than in the S7-8 group (7 [6-20] vs. 6 [6-9], P = 0.003). Post-hepatectomy liver failure including severe grades was more frequent in the RH group (43.9% vs. 10%, P = 0.008). In the S7-8 group, two patients with direct RHV reconstruction had RHV anastomosis obstruction, and eventually required insertion of a metallic stent. However, computed tomography performed 4 weeks after the operation showed intact venous outflow of the right liver in the S7-8 group. CONCLUSION: S7-8 can be performed safely in selected patients with a thick IRHV. For patients with no obvious IRHV, RHV reconstruction could be a good surgical strategy to retain venous outflow of the right liver with feasible outcomes.

Hepatic venous Doppler assessment can anticipate simplified pulmonary embolism severity index and right ventricle dysfunction in patients with acute pulmonary embolism.

PURPOSE: Acute pulmonary embolism (APE) is a life-threating cardiothoracic thromboembolic emergency in which right ventricle dysfunction (RVD) is a major concern. In the present study, we examined the hepatic veins (HVs) blood flow with pulsed-wave spectral Doppler ultrasonography to determine its relationship with the simplified pulmonary embolism severity index (sPESI) and the patient's RVD status. METHODS: We divided the 243 patients who met the inclusion criteria into two groups based on both their sPESI scores and their RVD status. Transthoracic echocardiography was performed to evaluate the RVD and the HVs within 1 hour after patient admission. The liver was evaluated using subcostal and intercostal echocardiographic windows in grayscale B-mode, and HVs were assessed using color and spectral Doppler assessment though the same echocardiographic windows. RESULT: A cut-off value of the systolic reverse flow velocity-time integral (SrVTI) = 2.2 cm carried a sensitivity and specificity of 84.29% and 74.89%, respectively, for the prediction of sPESI ≥ 1. A SrVTI cut-off value of 2.1 cm yielded a sensitivity and specificity of 83.03% and 73.91%, respectively, for the prediction of RVD. CONCLUSION: HV Doppler assessment could be a useful method for anticipating the sPESI and the presence of RVD in patients with APE. In addition, it may provide information regarding the hemodynamic impact of APE.

4D Flow MR Imaging to Improve Microwave Ablation Prediction Models: A Feasibility Study in an In Vivo Porcine Liver.

PURPOSE: To characterize the effect of hepatic vessel flow using 4-dimensional (4D) flow magnetic resonance (MR) imaging and correlate their effect on microwave ablation volumes in an in vivo non-cirrhotic porcine liver model. MATERIALS AND METHODS: Microwave ablation antennas were placed under ultrasound guidance in each liver lobe of swine (n = 3 in each animal) for a total of 9 ablations. Pre- and post-ablation 4D flow MR imaging was acquired to quantify flow changes in the hepatic vasculature. Flow measurements, along with encompassed vessel size and vessel-antenna spacing, were then correlated with final ablation volume from segmented MR images. RESULTS: The linear regression model demonstrated that the preablation measurement of encompassed hepatic vein size (ß = -0.80 ± 0.25, 95% confidence interval [CI] -1.15 to -0.22; P = .02) was significantly correlated to final ablation zone volume. The addition of hepatic vein flow rate found via 4D flow MRI (ß = -0.83 ± 0.65, 95% CI -2.50 to 0.84; P = .26), and distance from antenna to hepatic vein (ß = 0.26 ± 0.26, 95% CI -0.40 to 0.92; P = .36) improved the model accuracy but not significantly so (multivariate adjusted R2 = 0.70 vs univariate (vessel size) adjusted R2 = 0.63, P = .24). CONCLUSIONS: Hepatic vein size in an encompassed ablation zone was found to be significantly correlated with final ablation zone volume. Although the univariate 4D flow MR imaging-acquired measurements alone were not found to be statistically significant, its addition to hepatic vein size improved the accuracy of the ablation volume regression model. Pre-ablation 4D flow MR imaging of the liver may assist in prospectively optimizing thermal ablation treatment.

Hemodynamic Effects of Adding Simvastatin to Carvedilol for Primary Prophylaxis of Variceal Bleeding: A Randomized Controlled Trial.

INTRODUCTION: Beta-blockers are the mainstay agents for portal pressure reduction and to modestly reduce hepatic venous pressure gradient (HVPG). We studied whether addition of simvastatin to carvedilol in cirrhotic patients for primary prophylaxis improves the hemodynamic response. METHODS: Cirrhotic patients with esophageal varices and with baseline HVPG > 12 mm Hg were prospectively randomized for primary prophylaxis to receive either carvedilol (group A, n = 110) or carvedilol plus simvastatin (group B, n = 110). Primary objective was to compare hemodynamic response (HVPG reduction of ≥20% or <12 mm Hg) at 3 months, and secondary objectives were to compare first bleed episodes, death, and adverse events. RESULTS: The groups were comparable at baseline. The proportion of patients achieving HVPG response at 3 months was comparable between groups (group A-36/62 [58.1%], group B-36/59 [61%], P = 0.85). The degree of mean HVPG reduction (17.3% and 17.8%, respectively, P = 0.98) and hemodynamic response (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.43-1.83, P = 0.74) was also not different between the groups. Patients who achieved target heart rate with no hypotensive episodes in either group showed better hemodynamic response (77.8% vs 59.2%, P = 0.04). Failure to achieve target heart rate (OR: 0.48; 95% CI: 0.22-1.06) and Child C cirrhosis (OR: 4.49; 95% CI: 1.20-16.8) predicted nonresponse. Three (3.7%) patients on simvastatin developed transient transaminitis and elevated creatine phosphokinase and improved with drug withdrawal. Two patients in each group bled (P = 0.99). Three patients and 1 patient, respectively, in group A and B died (P = 0.32), with sepsis being the cause of death. DISCUSSION: Addition of simvastatin to carvedilol for 3 months for primary prophylaxis of variceal bleeding does not improve hemodynamic response over carvedilol monotherapy. Simvastatin usage should be closely monitored for adverse effects in Child C cirrhotic patients.

A Prognostic Strategy Based on Stage of Cirrhosis and HVPG to Improve Risk Stratification After Variceal Bleeding.

BACKGROUND AND AIMS: A hepatic venous pressure gradient (HVPG) decrease of 20% or more (or ≤12 mm Hg) indicates a good prognosis during propranolol/nadolol treatment but requires two HVPG measurements. We aimed to simplify the risk stratification after variceal bleeding using clinical data and HVPG. METHODS: A total of 193 patients with cirrhosis (62% with ascites and/or hepatic encephalopathy [HE]) who were within 7 days of bleeding had their HVPG measured before and at 1-3 months of treatment with propranolol/nadolol plus endoscopic band ligation. The endpoints were rebleeding and rebleeding/transplantation-free survival for 4 years. Another cohort (n = 231) served as the validation set. RESULTS: During follow-up, 45 patients had variceal bleeding and 61 died. The HVPG responders (n = 71) had lower rebleeding risk (10% vs. 34%, P = 0.001) and better survival than the 122 nonresponders (61% vs. 39%, P = 0.001). Patients with HE (n = 120) had lower survival than patients without HE (40% vs. 63%, P = 0.005). Among the patients with ascites/HE, those with baseline HVPG ≤ 16 mm Hg (n = 16) had a low rebleeding risk (13%). In contrast, among patients with ascites/HE and baseline HVPG > 16 mm Hg, only the HVPG responders (n = 32) had a good prognosis, with lower rebleeding risk and better survival than the nonresponders (n = 72) (respective proportions: 7% vs. 39%, P = 0.018; 56% vs. 30% P = 0.010). These findings allowed us to develop a strategy for risk stratification in which HVPG response was measured only in patients with ascites and/or HE and baseline HVPG > 16 mm Hg. This method reduced the "gray zone" (i.e., high-risk patients who had not died on follow-up) from 46% to 35% and decreased the HVPG measurements required by 42%. The validation cohort confirmed these results. CONCLUSIONS: Restricting HVPG measurements to patients with ascites/HE and measuring HVPG response only if the patient's baseline HVPG is over 16 mm Hg improves detection of high-risk patients while markedly reducing the number of HVPG measurements required.

Ectopic Balloon Device Placement to Correct the Positional Hepatic Venous Outflow Obstruction in Liver Transplantation.

OBJECTIVES: Hepatic vein outflow obstruction in liver transplantation can lead to graft or patient loss. We used an intrauterine balloon to overcome this complication in 13 liver transplant recipients. Here, we report the results of these cases; our report, as far as we know, involves the highest number of patients on this issue. MATERIALS AND METHODS: Positional hepatic vein outflow obstruction was diagnosed in 13 of 651 liver transplant recipients between January 2014 and December 2016. The grafts were repositioned by intrauterine balloon placed to the right subdiaphragmatic area. Data of donors, recipients, and grafts and postoperative courses were analyzed. RESULTS: Of the 13 patients, 9 were men, with age range of patients of 22 to 70 years. The amount of saline used to inflate the balloon was variable (200-450 cm3), and hepatic vein outflow obstruction was relieved after balloon implantation in all patients. There were no balloon-related complications. Removal was done at bedside, without any additional sedation or any additional skin incision on days 2 to 15. Doppler ultrasonography scans were performed before and after the balloon removal. There were no vascular complications after removal. CONCLUSIONS: Intrauterine balloon can be safely and efficiently used for hepatic vein outflow obstruction during liver transplant when needed.

Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon-Free Therapy.

BACKGROUND AND AIMS: Sustained virologic response (SVR) to interferon (IFN)-free therapies ameliorates portal hypertension (PH); however, it remains unclear whether a decrease in hepatic venous pressure gradient (HVPG) after cure of hepatitis C translates into a clinical benefit. We assessed the impact of pretreatment HVPG, changes in HVPG, and posttreatment HVPG on the development of hepatic decompensation in patients with PH who achieved SVR to IFN-free therapy. Moreover, we evaluated transient elastography (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolution of PH. APPROACH AND RESULTS: The study comprised 90 patients with HVPG ≥ 6 mm Hg who underwent paired HVPG, TE, and VITRO assessments before (baseline [BL]) and after (follow-up [FU]) IFN-free therapy. FU HVPG but not BL HVPG predicted hepatic decompensation (per mm Hg, hazard ratio, 1.18; 95% confidence interval, 1.08-1.28; P < 0.001). Patients with BL HVPG ≤ 9 mm Hg or patients who resolved clinically significant PH (CSPH) were protected from hepatic decompensation. In patients with CSPH, an HVPG decrease ≥ 10% was similarly protective (36 months, 2.5% vs. 40.5%; P < 0.001) but was observed in a substantially higher proportion of patients (60% vs. 24%; P < 0.001). Importantly, the performance of noninvasive methods such as TE/VITRO for diagnosing an HVPG reduction ≥ 10% was inadequate for clinical use (area under the receiver operating characteristic curve [AUROC],  < 0.8), emphasizing the need for HVPG measurements. However, TE/VITRO were able to rule in or rule out FU CSPH (AUROC, 0.86-0.92) in most patients, especially if assessed in a sequential manner. CONCLUSIONS: Reassessment of HVPG after SVR improved prognostication in patients with pretreatment CSPH. An "immediate" HVPG decrease ≥ 10% was observed in the majority of these patients and was associated with a clinical benefit, as it prevented hepatic decompensation. These results support the use of HVPG as a surrogate endpoint for interventions that lower portal pressure by decreasing intrahepatic resistance.