T-cell exhaustion and residency dynamics inform clinical outcomes in hepatocellular carcinoma.

BACKGROUND & AIMS: Despite recent translation of immunotherapies into clinical practice, the immunobiology of hepatocellular carcinoma (HCC), in particular the role and clinical relevance of exhausted and liver-resident T cells remain unclear. We therefore dissected the landscape of exhausted and resident T cell responses in the peripheral blood and tumor microenvironment of patients with HCC. METHODS: Lymphocytes were isolated from the blood, tumor and tumor-surrounding liver tissue of patients with HCC (n = 40, n = 10 treated with anti-PD-1 therapy). Phenotype, function and response to anti-PD-1 were analyzed by mass and flow cytometry ex vivo and in vitro, tissue residence was further assessed by immunohistochemistry and imaging mass cytometry. Gene signatures were analyzed in silico. RESULTS: We identified significant enrichment of heterogeneous populations of exhausted CD8+ T cells (TEX) in the tumor microenvironment. Strong enrichment of severely exhausted CD8 T cells expressing multiple immune checkpoints in addition to PD-1 was linked to poor progression-free and overall survival. In contrast, PD-1 was also expressed on a subset of more functional and metabolically active CD103+ tissue-resident memory T cells (TRM) that expressed few additional immune checkpoints and were associated with better survival. TEX enrichment was independent of BCLC stage, alpha-fetoprotein levels or age as a variable for progression-free survival in our cohort. These findings were in line with in silico gene signature analysis of HCC tumor transcriptomes from The Cancer Genome Atlas. A higher baseline TRM/TEX ratio was associated with disease control in anti-PD-1-treated patients. CONCLUSION: Our data provide information on the role of peripheral and intratumoral TEX-TRM dynamics in determining outcomes in patients with HCC. The dynamics between exhausted and liver-resident T cells have implications for immune-based diagnostics, rational patient selection and monitoring during HCC immunotherapies. LAY SUMMARY: The role of the immune response in hepatocellular carcinoma (HCC) remains unclear. T cells can mediate protection against tumor cells but are frequently dysfunctional and exhausted in cancer. We found that patients with a predominance of exhausted CD8+ T cells (TEX) had poor survival compared to patients with a predominance of tissue-resident memory T cells (TRM). This correlated with the molecular profile, metabolic and functional status of these cell populations. The enrichment of TEX was independently associated with prognosis in addition to disease stage, age and tumor markers. A high TRM proportion was also associated with better outcomes following checkpoint therapy. Thus, these T-cell populations are novel biomarkers with relevance in HCC.

Evaluation of Laboratory and Sonographic Parameters for Detection of Portal Hypertension in Patients with Common Variable Immunodeficiency.

Timely detection of portal hypertension as a manifestation in a subgroup of patients with common variable immunodeficiency (CVID) represents a challenge since it is usually not associated with liver cirrhosis. To identify relevant markers for portal hypertension, we evaluated clinical history, laboratory parameters, and abdominal ultrasound including liver elastography and biomarkers of extracellular matrix formation. Twenty seven (6%) of 479 CVID patients presented with clinically significant portal hypertension as defined by either the presence of esophageal varices or ascites. This manifestation occurred late during the course of the disease (11.8 years after first diagnosis of CVID) and was typically part of a multiorgan disease and associated with a high mortality (11/27 patients died during follow up). The strongest association with portal hypertension was found for splenomegaly with a longitudinal diameter of > 16 cm. Similarly, most patients presented with a liver stiffness measurement (LSM) of above 6.5 kPa, and a LSM above 20 kPa was always indicative of manifest portal hypertension. Additionally, many laboratory parameters including Pro-C4 were significantly altered in patients with portal hypertension without clearly increasing the discriminatory power to detect non-cirrhotic portal hypertension in CVID. Our data suggest that a spleen size above 16 cm and an elevated liver stiffness above 6.5 kPa should prompt further evaluation of portal hypertension and its sequelae, but earlier and better liquid biomarkers of this serious secondary complication in CVID are needed.

Implantation of transjugular intrahepatic portosystemic shunt (TIPS): indication and patient selection.

PURPOSE OF REVIEW: This review summarizes indications and contraindications for implantation of transjugular intrahepatic portosystemic shunt (TIPS). Further, patient selection strategies are discussed. RECENT FINDINGS: TIPS implantation is a highly effective treatment for portal hypertension. Main indications are ascites and variceal bleeding in patients with liver cirrhosis. There is growing evidence that early TIPS implantation after variceal bleeding is associated with an improved survival (preemptive TIPS).Preliminary data also suggest that an analogous concept of early TIPS implantation may be beneficial for patients with ascites. Further, well-selected patients with acute or chronic nonmalignant portal vein thrombosis can be effectively treated with TIPS implantation. In contrast, there is generally no recommendation for TIPS implantation in patients with hepatic veno-occlusive disease, noncirrhotic portal hypertension or prior before surgery to avoid complications of portal hypertension. Apart from evidence-based patient selection, the newly developed FIPS score can be an objective component in decision-making. SUMMARY: Consideration of well-established indications and contraindications for TIPS implantation as well as concise patient selection criteria are essential for an optimal outcome after TIPS implantation.

Reduction of esophageal stent migration rate with a novel over-the-scope fixation device (with video).

BACKGROUND AND AIMS: Self-expandable metal stent (SEMS) placement is routinely performed in a variety of benign and malignant GI diseases. One of the most frequent adverse events after esophageal SEMS placement is stent migration. We evaluated a novel over-the-scope clip device (stentfix OTSC; Ovesco Endoscopy, Tuebingen, Germany) designed and approved for SEMS fixation. METHODS: This single-center retrospective observational cohort study was performed to analyze stent migration rates before and after availability of the stentfix OTSC device. A cohort of patients who consecutively underwent SEMS fixation with the stentfix OTSC system (SF cohort) was compared with an historical cohort of patients who did not receive stentfix OTSC fixation or any other stent fixation method (NF cohort) before the stentfix OTSC system became available. Outcome variables including technical success, adverse events and clinical success were analyzed. RESULTS: Seventy-seven patients (SF cohort, 26; NF cohort, 51) underwent esophageal SEMS implantation for malignant (69%) and benign (31%) conditions. The technical success rate of stent fixation was 100%, and no procedure-related adverse events were observed. The stent migration rate was significantly lower in the SF cohort compared with the NF cohort (8.3% vs 35.4%, P < .001), indicating a relative risk reduction of 76.5% associated with stentfix OTSC application. Stent implantation across the gastroesophageal junction was identified as a predictor of stent migration. CONCLUSIONS: In patients with benign or malignant gastroesophageal diseases, there was a significantly lower stent migration rate in patients managed with the stentfix OTSC system compared with those without stent fixation. The application was technically successful in all cases, and no adverse events related to clip application or removal were observed.

TIPS for the management of stomal variceal bleeding due to cirrhotic and non-cirrhotic portal hypertension.

BACKGROUND: Portal hypertension (PH) is associated with the development of esophageal or gastric varices, which can cause bleedings with high mortality. Varices can also manifest at sites of stomata. These parastomal varices can cause recurrent variceal bleedings (VB) despite local therapies. We present a case series of parastomal VB due to PH that were managed with implantation of transjugular intrahepatic portosystemic shunt (TIPS). METHODS: We retrospectively included all patients (pt) from 2 tertiary medical centers with parastomal VB between January 2014 and February 2020 who underwent the TIPS procedure. RESULTS: Nine pt were included. Seven pt had liver cirrhosis, mostly alcohol-related. Two pt had non-cirrhotic PH due to porto-sinusoidal vascular disease (PSD). Four pt had a colostomy, 1 an ileostomy, and 4 an ileal conduit. Malignancy was the leading cause of stoma surgery. All 9 pt suffered from recurrent parastomal VB despite non-selective beta-blocker and/or local therapy (e.g., compression, coagulation, suture ligation, or surgical stoma revision). All pt received TIPS implantation. In 7 pt, TIPS implantation led to sustainable hemostasis. Two pt suffered a bleeding relapse that was attributable to TIPS dysfunction. TIPS revision with coil embolization of the varices terminated the VB sustainably in both pt. CONCLUSIONS: In pt presenting with recurrent stomal bleedings, parastomal varices as a rare complication of PH must be taken into consideration as an underlying cause. In our case series, we managed to sustainably cease parastomal VB by TIPS implantation with or without coil embolization of the ectopic varices.

IL-2 contributes to cirrhosis-associated immune dysfunction by impairing follicular T helper cells in advanced cirrhosis.

BACKGROUND & AIMS: Patients with decompensated cirrhosis suffer from recurrent infections and inadequate responses to prophylactic vaccinations. However, many patients present with hypergammaglobulinemia (HGG), indicating a sustained ability to generate antibody responses. As follicular T helper (Tfh) cells are central facilitators of humoral immunity, we hypothesized that Tfh cell responses may be altered in advanced liver disease and we aimed to identify the mechanisms underlying any such alterations. METHODS: Tfh, regulatory T (Treg) cells, B cells, circulating cytokines and immunoglobulins were analyzed in cohorts of patients with compensated (n = 37) and decompensated cirrhosis (n = 82) and in non-cirrhotic controls (n = 45). Intrahepatic T cells were analyzed in 8 decompensated patients. The influence of IL-2 on Tfh cell function was evaluated in vitro, including Tfh cell cloning and T cell-B cell co-cultures with clones and primary tonsil-derived Tfh cells. RESULTS: Tfh cell frequencies were reduced in patients with decompensated cirrhosis, with phenotypic signatures indicative of increased IL-2 signaling. Soluble IL-2 receptor (sCD25) was elevated in these patients and CD4 T cells were more responsive to IL-2 signaling, as characterized by STAT5 phosphorylation. IL-2 exposure in vitro diminished the Tfh phenotype and resulted in impaired Tfh helper function in co-culture experiments with naïve B cells. Tfh cells were barely detectable in cirrhotic livers. IL-2 signatures on Tfh cells in decompensated patients correlated with immunoglobulin levels, which were found to be associated with improved survival. CONCLUSIONS: Tfh cell impairment represents a previously underestimated feature of cirrhosis-associated immune dysfunction that is driven by IL-2. The presence of HGG in decompensated patients predicts an intact Tfh cell compartment and is associated with a favorable outcome. LAY SUMMARY: Patients with advanced cirrhosis often fail to generate protective immunity after prophylactic vaccinations and suffer from recurring infections that are associated with high mortality. Follicular T helper (Tfh) cells are specialized CD4 T cells that enable the emergence of antibody responses against microbial pathogens. This report demonstrates that Tfh cells are impaired in patients with advanced cirrhosis due to interleukin-2 signaling, a cytokine that is known to impair the generation of Tfh cells.

Refining prediction of survival after TIPS with the novel Freiburg index of post-TIPS survival.

BACKGROUND & AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an effective and safe treatment for complications of portal hypertension. Survival prediction is important in these patients as they constitute a high-risk population. Therefore, the aim of our study was to develop an alternative prognostic model for accurate survival prediction after planned TIPS implantation. METHODS: A total of 1,871 patients with de novo TIPS implantation for ascites or secondary prophylaxis of variceal bleeding were recruited retrospectively. The study cohort was divided into a training set (80% of study patients; n = 1,496) and a validation set (20% of study patients; n = 375). Further, patients with early (preemptive) TIPS implantation due to variceal bleeding were included as another validation cohort (n = 290). Medical data and overall survival (OS) were assessed. A Cox regression model was used to create an alternative prediction model, which includes significant prognostic factors. RESULTS: Age, bilirubin, albumin and creatinine were the most important prognostic factors. These parameters were included in a new score named the Freiburg index of post-TIPS survival (FIPS). The FIPS score was able to identify high-risk patients with a significantly reduced median survival of 5.0 (3.1-6.9) months after TIPS implantation in the training set. These results were confirmed in the validation set (median survival of 3.1 [0.9-5.3] months). The FIPS score showed better prognostic discrimination compared to the Child-Pugh, MELD, MELD-Na score and the bilirubin-platelet model. However, the FIPS score showed insufficient prognostic discrimination in patients with early TIPS implantation. CONCLUSIONS: The FIPS score is superior to established scoring systems for the identification of high-risk patients with a worse prognosis following elective TIPS implantation. LAY SUMMARY: Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is a safe and effective treatment for patients with cirrhosis and clinically significant portal hypertension. However, risk stratification is a major challenge in these patients as currently available scoring systems have major drawbacks. Age, bilirubin, albumin and creatinine were included in a new risk score which was named the Freiburg index of post-TIPS survival (FIPS). The FIPS score can identify patients at high risk and may guide clinical decision making.

Contrast-Enhanced Ultrasound Algorithms (CEUS-LIRADS/ESCULAP) for the Noninvasive Diagnosis of Hepatocellular Carcinoma - A Prospective Multicenter DEGUM Study.

BACKGROUND: This prospective multicenter study funded by the DEGUM assesses the diagnostic accuracy of standardized contrast-enhanced ultrasound (CEUS) for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients. METHODS: Patients at high risk for HCC with a histologically proven focal liver lesion on B-mode ultrasound were recruited prospectively in a multicenter approach. Clinical and imaging data were entered via online entry forms. The diagnostic accuracies for the noninvasive diagnosis of HCC were compared for the conventional interpretation of standardized CEUS at the time of the examination (= CEUS on-site) and the two CEUS algorithms ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) and CEUS LI-RADS (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System). RESULTS: 321 patients were recruited in 43 centers; 299 (93.1 %) had liver cirrhosis. The diagnosis according to histology was HCC in 256 cases, and intrahepatic cholangiocarcinoma (iCCA) in 23 cases. In the subgroup of cirrhotic patients (n = 299), the highest sensitivity for the diagnosis of HCC was achieved with the CEUS algorithm ESCULAP (94.2 %) and CEUS on-site (90.9 %). The lowest sensitivity was reached with the CEUS LI-RADS algorithm (64 %; p < 0.001). However, the specificity of CEUS LI-RADS (78.9 %) was superior to that of ESCULAP (50.9 %) and CEUS on-site (64.9 %; p < 0.001). At the same time, the negative predictive value (NPV) of CEUS LI-RADS was significantly inferior to that of ESCULAP (34.1 % vs. 67.4 %; p < 0.001) and CEUS on-site (62.7 %; p < 0.001). The positive predictive values of all modalities were high (around 90 %), with the best results seen for CEUS LI-RADS and CEUS on-site. CONCLUSION: This is the first multicenter, prospective comparison of standardized CEUS and the recently developed CEUS-based algorithms in histologically proven liver lesions in cirrhotic patients. Our results reaffirm the excellent diagnostic accuracy of CEUS for the noninvasive diagnosis of HCC in high-risk patients. However, on-site diagnosis by an experienced examiner achieves an almost equal diagnostic accuracy compared to CEUS-based diagnostic algorithms.

[30 Years of Transjugular Intrahepatic Portosystemic Shunt (TIPS): casting a retrospective glance and future perspectives]. / 30 Jahre transjugulärer intrahepatischer portosystemischer Shunt (TIPS) ­ Rückblick und Perspektive.

For 30 years the transjugular intrahepatic portosystemic shunt (TIPS) is successfully used for the treatment of portal hypertension. Indication for TIPS in relation to variceal bleeding and refractory ascites is scientifically documented and defined by national and international guidelines. For rare indications such as hepatorenal syndrome, portal vein thrombosis or the neodjuvant TIPS larger evidence-based studies are missing. An important contraindication and the leading clinical complication after TIPS is the development of hepatic encephalopathy (HE). Reduction of post-TIPS HE is therefore aimed through development of further technical enhancements of the TIPS-stents.

Repeated SBRT for in- and out-of-field recurrences in the liver.

PURPOSE: To evaluate the feasibility and toxicity profile of repeated stereotactic body radiotherapy (SBRT) for recurrent primary or secondary liver tumors. METHODS: Consecutive patients with primary (hepatocellular carcinoma [HCC] or cholangiocarcinoma [CCC]) or secondary liver cancer (LM), with intrahepatic recurrence or progression after SBRT, underwent re-SBRT in 3 to 12 fractions with a median time of 15 (range 2-66) months between treatments. RESULTS: In all, 24 patients which were previously treated with SBRT (30 lesions) were retreated with SBRT for "in- and out-of-field" recurrences (2nd SBRT: n = 28, 3rd SBRT: n = 2). The median follow-up after re-irradiation was 14 months. The median prescribed dose for the first SBRT was 46.5 (range 33-66 Gy, EQD210 = 70.5) Gy and 48 (range 27-66 Gy, EQD210 = 71) Gy for the re-SBRT. The median mean liver dose (Dmean, liver) was 6 Gy (range 1-25, EQD22 = 7 Gy) for the first SBRT and 10 Gy (range 1-63 Gy, EQD22 = 9 Gy) for the re-SBRT. Of the 30 re-irradiated lesions 6 were re-irradiated in-field resulting in a median EQD22, maximum of 359 (range 120-500) Gy for both treatments, with an α/ß = 2 to account for liver parenchyma. Treatment was well tolerated. Two patients with stent placement before SBRT developed cholangitis 4 and 14 months after re-SBRT. There were no elevations of the serum liver parameters after re-SBRT. One patient developed a grade 3 gastrointestinal bleeding. There was no radiation induced liver disease (RILD) observed. CONCLUSIONS: Repeated liver SBRT is feasible, without excessive liver toxicity, when there is no considerable overlapping with pre-irradiated portions of the stomach or bowel and enough time for the liver to regenerate.

The role of albumin-bilirubin grade and inflammation-based index in patients with hepatocellular carcinoma treated with stereotactic body radiotherapy.

PURPOSE: We evaluated the prognostic accuracy of the albumin-bilirubin (ALBI) grade and the inflammation-based index (IBI) in estimating overall survival (OS) and toxicity in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Forty patients with 47 HCC lesions with a Barcelona Clinic Liver Cancer (BCLC) classification stage B or C were treated with SBRT in 3-12 fractions. The ALBI grade and the IBI were calculated at different time points (baseline, during, at the end of treatment and at follow-up) and compared with the Child-Pugh (CP) score as well as other patient- and treatment-related parameters, concerning OS and toxicity. RESULTS: The median follow-up was 14.3 months for patients alive. The median OS from SBRT was 10 (95% confidence interval 8.3-11.6) months. The local control at 1 year was 79%. A lower IBI during treatment was associated with better OS (p = 0.034) but not CP and ALBI. Higher C­reactive protein levels as well as higher alpha-fetoprotein concentrations correlated with worse survival (p = 0.001). Both higher ALBI (p = 0.02) and CTP (p = 0.001) at baseline correlated with a higher incidence of acute and late toxicities (CTC ≥2). Neither the mean radiation dose to the liver nor the dose to 700 cc of the liver correlated with the occurrence of toxicities. CONCLUSIONS: In this analysis, a higher ALBI grade as well as a higher CP were predictors of higher incidence of toxicity, whereas a lower IBI during treatment correlated with a better OS. These results should be further evaluated in prospective studies.

Comparison of local tumor control in patients with HCC treated with SBRT or TACE: a propensity score analysis.

BACKGROUND: As stereotactic body radiation therapy (SBRT) has shown to be effective and safe in patients with hepatocellular carcinoma (HCC), the aim of our propensity score matched analysis was to evaluate the efficacy of SBRT in comparison to transarterial chemoembolization (TACE) in intermediate and advanced HCC. METHODS: Patients treated with TACE (n = 367) and patients allocated to SBRT (n = 35) were enrolled in this study. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics of TACE and SBRT patients. Local tumor control (LC) 1 year after treatment, overall survival (OS) and 1-year mortality were assessed. RESULTS: Patients treated with SBRT have received more prior HCC treatments compared to TACE patients. The LC 1 year after treatment in the unmatched cohort was 74.4% for TACE patients compared to 84.8% in the SBRT group. Patients treated with TACE showed significantly improved OS (17.0 months vs. 9.0 months, p = 0.016). After propensity score matching, the LC in the TACE (n = 70) and SBRT (n = 35) group was comparable (82.9% vs. 84.8%, p = 0.805) and OS did not differ significantly in both groups. CONCLUSIONS: SBRT after prior HCC therapy in selected patients shows comparable LC at 1 year, OS and 1-year mortality compared to patients treated with TACE.

Lopinavir serum concentrations of critically ill infants: a pharmacokinetic investigation in South Africa.

The role of therapeutic drug monitoring in pediatric antiretroviral therapy is unclear. A little pharmacokinetic datum from clinical practice exists beyond controlled approval studies including clinically stable children. The aim of this study is to quantify LPV exposure of critically ill infants in an ICU and-by identifying risk factors for inadequate exposure-to define sensible indications for TDM in pediatric HIV care; in addition, assume total drug adherence in ICU to compare LPV exposure with a setting of unknown adherence. In this prospective investigation, 15 blood samples from critically ill infants in the pediatric ICU at Tygerberg Hospital were analyzed for LPV-serum concentrations. They were then compared to those of 22 blood samples from out-patient children. Serum-level measurements were performed with an established high-performance liquid chromatography method. All LPV-serum levels of ICU patients were higher than a recommended Ctrough (= 1.000 ng/ml), 60% of levels were higher than Cmax (8.200 ng/ml). Partly, serum levels reached were extremely high (Maximum: 28.778 ng/ml). Low bodyweight and age correlated significantly with high LPV concentrations and were risk factors for serum levels higher than Cmax. Significantly fewer serum levels from infants in ICU care (mean: 11.552 ng/ml ± SD 7760 ng/ml) than from out-patient children (mean: 6.756 ng/ml ± SD 6.003 ng/ml) were subtherapeutic (0 vs. 28%, p = 0.008). Under total adherence in the ICU group, there were no subtherapeutic serum levels, while, in out-patient, children with unknown adherence 28% of serum levels were found subtherapeutic. Low bodyweight and age are risk factors for reaching potentially toxic LPV levels in this extremely fragile population. TDM can be a reasonable tool to secure sufficient and safe drug exposure in pediatric cART.

Survival benefit of transarterial chemoembolization in patients with metastatic hepatocellular carcinoma: a single center experience.

BACKGROUND: As prognosis of patients with metastatic hepatocellular carcinoma (HCC) is mainly determined by intrahepatic HCC progression, local treatment with TACE may result in improved OS, although it is not recommended. The purpose of this study was to analyze retrospectively the efficacy of TACE and its impact on OS in patients with metastatic hepatocellular carcinoma (HCC). METHODS: Two hundred and fifteen patients with metastatic HCC who were treated at our Liver Center between 2003 and 2014 were included in this retrospective analysis. Medical records, laboratory parameters and imaging studies were analyzed. Treatment of metastatic HCC and OS were assessed RESULTS: One hundred and two patients (47.4%) did not receive any HCC specific treatment while 48 patients (22.3%) were treated with sorafenib, 42 patients (19.5%) with TACE and 23 patients (10.7%) received treatment with TACE and sorafenib in combination. Survival analyses and Cox regression models revealed that TACE and a combination therapy of TACE and sorafenib were significant prognostic factors in metastatic HCC. However, further analyses revealed that there was no additional prognostic effect of adding sorafenib to TACE treatment in this patient cohort. CONCLUSIONS: In metastatic HCC, treatment of intrahepatic tumor by TACE may be associated with improved survival. These results support the prognostic importance of treating intrahepatic HCC even in patients with metastatic disease. Therefore, we suggest evaluating the technical feasibility of TACE in all metastatic patients.

Free Hepatic Vein Pressure Is Not Useful to Calculate the Portal Pressure Gradient in Cirrhosis: A Morphologic and Hemodynamic Study.

PURPOSE: To systematically evaluate the accuracy of free hepatic vein pressure (FHVP), the internal reference for hepatic venous pressure gradient (HVPG). MATERIALS AND METHODS: Diameter and pressure measurements were obtained in multiple locations within the hepatic vein, inferior vena cava (IVC), and right atrium on 30 hepatic venograms in 29 consecutive candidates for transjugular intrahepatic portosystemic shunt creation. RESULTS: On angiography, 15 patients (52%) had hepatic veins showing a normal and conical appearance, whereas the other 14 had irregular or narrow (maximal diameter ≤ 6 mm) veins. Diameters of hepatic veins increased from 4.4 mm ± 0.9 (range, 3.3-7 mm) at a peripheral position to 8.7 mm ± 3.0 (range, 5.0-15.5 mm; P < .001) at a central position, and respective pressures decreased from 10.9 mm Hg ± 3.7 (range, 3-17 mm Hg) to 7.4 mm Hg ± 3.7 (range, 0-14 mm Hg; P < .001). Gradients between wedged hepatic vein pressure and central free hepatic vein, IVC, and right atrium pressures were 17.2 mm Hg ± 5.4 (range, 4-33 mm Hg), 18.0 mm Hg ± 5.8 (range, 4-33 mm Hg), and 20.0 mm Hg ± 5.9 (range, 4-33 mm Hg), respectively. Pearson correlation coefficients were 0.679 between the HVPG and hepatic atrial pressure gradient (HAPG) and 0.889 between the wedged hepatic vein/IVC pressure gradient (HCPG) and HAPG. CONCLUSIONS: FHVP measurement depends on catheter tip position and vein morphology. Its use to calculate HVPG is not recommended. The high agreement between the HCPG and the HAPG suggests that both gradients may be used if one considers a systemic difference of 2 mm Hg.

Effect of TIPS placement on portal and splanchnic arterial blood flow in 4-dimensional flow MRI.

OBJECTIVES: To assess changes in portal and splanchnic arterial haemodynamics in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) using four-dimensional (4D) flow MRI, a non-invasive, non-contrast imaging technique. METHODS: Eleven patients undergoing TIPS implantation were enrolled. K-t GRAPPA accelerated non-contrast 4D flow MRI of the liver vasculature was applied with acceleration factor R = 5 at 3Tesla. Flow analysis included three-dimensional (3D) blood flow visualization using time-resolved 3D particle traces and semi-quantitative flow pattern grading. Quantitative evaluation entailed peak velocities and net flows throughout the arterial and portal venous (PV) systems. MRI measurements were taken within 24 h before and 4 weeks after TIPS placement. RESULTS: Three-dimensional flow visualization with 4D flow MRI revealed good image quality with minor limitations in PV flow. Quantitative analysis revealed a significant increase in PV flow (562 ± 373 ml/min before vs. 1831 ± 965 ml/min after TIPS), in the hepatic artery (176 ± 132 ml/min vs. 354 ± 140 ml/min) and combined flow in splenic and superior mesenteric arteries (770 ml/min vs. 1064 ml/min). Shunt-flow assessment demonstrated stenoses in two patients confirmed and treated at TIPS revision. CONCLUSIONS: Four-dimensional flow MRI might have the potential to give new information about the effect of TIPS placement on hepatic perfusion. It may explain some unexpected findings in clinical observation studies. KEY POINTS: • 4D flow MRI, a non-invasive, non-contrast imaging technique, is feasible after TIPS. • Provides visualization and quantification of hepatic arterial, portal venous, collateral and TIPS haemodynamics. • Better understanding of liver blood flow changes after TIPS and patient management.