Evolution of spontaneous portosystemic shunts over time and following aetiological intervention in patients with cirrhosis.

Background & Aims: Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution. Methods: Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8 mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients. Results: A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% (p <0.001). Patients with worse liver function during follow-up showed a simultaneous aggravation in SPSS distribution. Non-cured patients (n = 191) experienced a significant worsening in liver function, more episodes of liver decompensation and lower transplant-free survival compared to cured patients (n = 191). However, no differences were observed regarding SPSS distribution at inclusion and at follow-up, with both groups showing a trend to worsening. Total shunt diameter increased more in non-cured (52%) than in cured patients (28%). However, total shunt area (TSA) significantly increased only in non-cured patients (74 to 122 mm2, p <0.001). Conclusions: The presence of SPSS in cirrhosis increases over time and parallels liver function deterioration. Aetiological intervention in these patients reduces liver-related complications, but SPSS persist although progression is decreased. Impact and implications: There is no information regarding the evolution of spontaneous portosystemic shunts (SPSS) during the course of cirrhosis, and especially after disease regression with aetiological interventions, such as HCV treatment with direct-acting antivirals or alcohol abstinence. These results are relevant for clinicians dealing with patients with cirrhosis and portal hypertension because they have important implications for the management of cirrhosis with SPSS after disease regression. From a practical point of view, physicians should be aware that in advanced cirrhosis with portal hypertension, after aetiological intervention, SPSS mostly persist despite liver function improvement, and complications related to SPSS may still develop.

Transversal psoas muscle thickness measurement is associated with response and survival in patients with HCC undergoing immunotherapy.

BACKGROUND: Sarcopenia is a common problem in patients with HCC. We aimed to evaluate the prognostic and predictive value of baseline transversal psoas muscle thickness (TPMT) measurement in patients with HCC undergoing immunotherapy. METHODS: HCC patients treated with programmed death ligand 1-based therapies between June 2016 and October 2022 at the Vienna General Hospital (n = 80) and the Hôpital Beaujon Clichy (n = 96) were included and followed until April 2023. TPMT at the level of the third lumbar vertebra was measured independently by 2 radiologists to evaluate interreader reliability. TPMT <12 mm/m in men and <8 mm/m in women indicated sarcopenia. RESULTS: Overall, 176 patients (age: 66.3±11.7 y; male: n=143, 81%, Barcelona-Clinic Liver Cancer C: n=121, 69%) were included, of which 131 (74%) exhibited cirrhosis. Interreader agreement for the diagnosis of sarcopenia based on TPMT was 92.6%, and Cohen κ showed a "strong agreement" [κ = 0.84 (95% CI: 0.75-0.92)]. Sarcopenia, present in 58 patients (33%), was associated with shorter median overall survival [7.2 (95% CI: 5.0-9.5) vs. 22.6 (95% CI: 16.4-28.8 months); p < 0.001] and median progression-free survival [3.4 (95% CI: 0.2-6.8) vs. 7.9 (95% CI: 5.8-9.9 months), p = 0.001], and an independent predictor of overall [adjusted HR: 1.63 (95% CI: 1.07-2.48)] and progression-free mortality [adjusted HR: 1.54 (95% CI: 1.06-2.23)] in multivariable analyses. The objective response rate [evaluable in 162 subjects (92.0%)] per modified Response Evaluation Criteria In Solid Tumors (mRECIST) in patients with and without sarcopenia was 22% and 39%, respectively (p = 0.029). Survival and radiological responses were worse in patients with sarcopenia and systemic inflammation [median overall survival: 6.1 (95% CI: 3.6-8.6) mo; median progression-free survival: 2.8 (95% CI: 2.1-3.4) mo; objective response rate=16%; disease control rate=39%]. CONCLUSIONS: Evaluation of sarcopenia using TPMT measurement is reliable and identifies HCC patients with a dismal prognosis and response to immunotherapy.

[Computed tomography and magnetic resonance imaging of colonic diseases]. / Dickdarmerkrankungen in Computertomographie und Magnetresonanztomographie.

BACKGROUND: Early diagnosis of a luminal colonic disease is of essential clinical importance to start timely optimised therapy and detect complications early. OBJECTIVES: This paper aims to provide an overview of the use of radiological methods in diagnosing neoplastic and inflammatory luminal diseases of the colon. Characteristic morphological features are discussed and compared. MATERIALS AND METHODS: Based on an extensive literature review, the current state of knowledge regarding the imaging diagnosis of luminal pathologies of the colon and their importance in patient management is presented. RESULTS: Technological advances in imaging have made the diagnosis of neoplastic and inflammatory colonic diseases using abdominal computed tomography and magnetic resonance imaging the established standard. Imaging is performed as part of the initial diagnosis in clinically symptomatic patients, to exclude complications, as a follow-up assessment under therapy and as an optional screening method in asymptomatic individuals. CONCLUSIONS: Accurate knowledge of the radiological manifestations of the numerous luminal disease patterns, the typical distribution pattern and characteristic bowel wall changes are essential to improve diagnostic decision-making.

[CT colonography : Technique and indications]. / CT-Kolonographie : Technik und Indikationen.

BACKGROUND: Dedicated radiological expertise and a high-quality examination, performed according to current technical standards and for accepted indications, are prerequisite to achieve excellent results with CT colonography (CTC). OBJECTIVES: The aim of this article is to review current standards of the examination technique as well as indications and contraindications for CTC based on recent recommendations and guidelines. MATERIALS AND METHODS: Based on extensive literature research, current knowledge about the examination technique and the indications and contraindications is summarized. RESULTS: CTC is the radiological examination of choice for the detection of colorectal neoplasia. Beside incomplete or refused colonoscopy and contraindications to colonoscopy, CTC is also a noninvasive option for opportunistic colorectal cancer screening. The examination technique is based on a CTC-specific patient preparation scheme that includes fecal tagging, colonic distension, low-dose CT scans in two patient positions and a combined 2D and 3D data evaluation. CONCLUSIONS: Performing CTC according to current technical standards is prerequisite for high-quality examinations and is, thus, also a key factor to obtain a correct diagnosis. CTC is a noninvasive examination, capable of providing clinically relevant diagnoses for a wide range of indications.

Outcome of Budd-Chiari Syndrome Patients Treated With Direct Oral Anticoagulants: An Austrian Multicenter Study.

BACKGROUND AND AIMS: Direct oral anticoagulants (DOACs) may simplify management of Budd-Chiari syndrome (BCS). Here, we report our experience with off-label use of DOACs for anticoagulation in BCS. METHODS: The safety of DOAC vs vitamin K antagonist treatment as well as associated clinical outcomes were retrospectively assessed in 47 BCS patients treated at 6 Austrian centers. RESULTS: Mean age at study inclusion was 37.9 ± 14.0 years and mean Model for End-Stage Liver Disease was 13.1 ± 5.1. Overall, 63.8% (n = 30) of patients had decompensated liver disease, and 87.2% (n = 41) showed clinical signs of portal hypertension. During a median follow-up of 82.5 (interquartile range, 43.1-121.8) months, 43 (91.5%) patients received anticoagulation alone or following interventional treatment, including 22 (46.8%) patients treated with DOACs (edoxaban: 10, apixaban: 4, rivaroxaban: 3, dabigatran: 3, more than one DOAC sequentially: 2) for a median of 24.4 (interquartile range, 5.7-35.1) months. While 72.7% (n = 16 of 22) of patients were switched from low-molecular-weight heparin (n = 12) or vitamin K antagonist (n = 4) to DOAC after disease stabilization or improvement, 27.3% (n = 6 of 22) of BCS patients were initially treated with DOAC. Complete response (European Association for the Study of the Liver criteria) was achieved or maintained in 14 (63.6%) of 22 patients, with ongoing response in 2 patients, while disease progressed in 6 patients (including 2 patients with hepatocellular carcinoma). Four major spontaneous bleedings (18.2%; incidence rate 8.8 per 100 patient-years; n = 2 upper gastrointestinal bleeding, n = 1 lower gastrointestinal bleeding, n = 1 hepatocellular carcinoma rupture), 7 minor bleedings, and 1 major procedure-related bleeding (4.5%; 2.2 per 100 patient-years) occurred during DOAC therapy. Overall transplant-free survival was 91.6% at 5 years. CONCLUSIONS: DOACs seem to be effective and safe for long-term anticoagulation in patients with BCS, but confirmation by larger prospective studies is needed.

Imaging features facilitate diagnosis of porto-sinusoidal vascular disorder.

OBJECTIVES: Porto-sinusoidal vascular disorder (PSVD) is a recently defined vascular liver disease. Since diagnosis remains challenging, we aimed to evaluate radiological features that are distinct between PSVD and cirrhosis. METHODS: Clinical, laboratory, and radiological parameters (CT/MRI) of patients with histologically-confirmed PSVD vs. cirrhosis vs. non-cirrhotic parenchymal liver disease were retrospectively evaluated. RESULTS: Sixty-three PSVD, 155 cirrhosis, and 41 non-cirrhotic patients were included. As compared to cirrhosis, PSVD patients were younger and had lower HVPG, liver stiffness, and MELD. Routine clinical and imaging findings indicative of portal hypertension were similarly common. Intrahepatic portal tract abnormalities (49% vs. 15%; p < 0.001), FNH-like lesions (30% vs. 1%; p < 0.001), and abnormal liver morphology defined as peripheral parenchymal atrophy and compensatory hypertrophy of central segments (32% vs. 7%; p < 0.001) were significantly more common in PSVD patients. Hypertrophy of segment I (70% vs. 84%; p = 0.019), atrophy of segment IV (24% vs. 47%; p = 0.001), and nodular liver surface (22% vs. 89%; p < 0.001) were more common in patients with cirrhosis. In patients with gadoxetic acid-enhanced MRI, we identified the distinct imaging feature of "periportal hyperintensity" in the hepatobiliary phase (HBP) in 42% of patients with PSVD (14/33) vs. 1% in cirrhosis (1/95) vs. 0% in non-cirrhotic controls (0/41); p < 0.001). CONCLUSIONS: Diagnosis of PSVD must be considered in younger patients presenting with clinical features of portal hypertension, portal tract abnormalities, and FNH-like lesions on CT/MRI. 'Periportal hyperintensity' in the HBP of gadoxetic acid-enhanced MRI was identified as a specific radiological feature of PSVD. KEY POINTS: • Cross-sectional imaging can provide essential information to identify patients with porto-sinusoidal vascular disorder (PSVD). • Intrahepatic portal tract abnormalities, FNH-like lesions, and abnormal liver morphology are common in PSVD patients. • Periportal hyperintensity on the hepatobiliary phase of gadoxetic acid-enhanced MRI seems to be specific for patients with PSVD.

Progressive cholestasis and associated sclerosing cholangitis are frequent complications of COVID-19 in patients with chronic liver disease.

BACKGROUND AND AIMS: Cholestasis is associated with disease severity and worse outcome in COVID-19. Cases of secondary sclerosing cholangitis (SSC) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been described. APPROACH AND RESULTS: Hospitalized patients with COVID-19 between 03/2020 and 07/2021 were included. Patients were stratified as having (i) no chronic liver disease (CLD), (ii) non-advanced CLD (non-ACLD), or (iii) advanced CLD (ACLD). Patients with CLD and non-COVID-19 pneumonia were matched to patients with CLD and COVID-19 as a control cohort. Liver chemistries before (Pre) and at first, second, and third blood withdrawal after SARS-CoV-2 infection (T1-T3) and at last available time point (last) were recorded. A total of 496 patients were included. In total, 13.1% (n = 65) had CLD (non-ACLD: 70.8%; ACLD: 29.2%); the predominant etiology was NAFLD/NASH (60.0%). COVID-19-related liver injury was more common among patients with CLD (24.6% vs. 10.6%; p = 0.001). After SARS-CoV-2 infection, patients with CLD exhibited progressive cholestasis with persistently increasing levels of alkaline phosphatase (Pre: 91.0 vs. T1: 121.0 vs. last: 175.0 U/L; p < 0.001) and gamma-glutamyl transferase (Pre: 95.0 vs. T1: 135.0 vs. last: 202.0 U/L; p = 0.001). A total of 23.1% of patients with CLD (n = 15/65) developed cholestatic liver failure (cholestasis plus bilirubin ≥6 mg/dl) during COVID-19, and 15.4% of patients (n = 10/65) developed SSC. SSC was significantly more frequent among patients with CLD and COVID-19 than in patients with CLD and non-COVID-19 pneumonia (p = 0.040). COVID-19-associated SSC occurred predominantly in patients with NAFLD/NASH and metabolic risk factors. A total of 26.3% (n = 5/19) of patients with ACLD experienced hepatic decompensation after SARS-CoV-2 infection. CONCLUSIONS: About 20% of patients with CLD develop progressive cholestasis after SARS-CoV-2 infection. Patients with NAFLD/NASH and metabolic risk factors are at particular risk for developing cholestatic liver failure and/or SSC after COVID-19.

Covered Transjugular Intrahepatic Portosystemic Shunt Improves Hypersplenism-Associated Cytopenia in Cirrhosis.

BACKGROUND: Patients with cirrhosis often develop portal hypertension-associated splenomegaly and hypersplenism, potentially causing severe cytopenia. AIMS: Systematic assessment on the impact of transjugular intrahepatic portosystemic shunt (TIPS) implantation on platelet count (PLT), hemoglobin (Hb), and white blood cell count (WBC). METHODS: Patients with cirrhosis undergoing covered TIPS implantation were retrospectively included. Patients with malignancies or hematologic disorders were excluded. Hematology lab work was recorded at baseline (pre-TIPS) and at regular intervals after TIPS. RESULTS: One hundred ninety-two patients (male: 72.4%, age: 56 ± 10 years; MELD: 12.1 ± 3.6) underwent TIPS implantation. Higher-grade (≥ G2) thrombocytopenia (PLT < 100 G/L) was present in 54 (28.7%), ≥ G2 anemia (Hb < 10 g/dL) in 57 (29.7%), and ≥ G2 leukopenia (WBC < 2 G/L) in 3 (1.6%) patients pre-TIPS, respectively. Resolution of ≥ G2 thrombocytopenia, anemia, and leukopenia occurred in 24/55 (43.6%), 23/57 (40.4%), and 2/3 (66.7%), respectively. Similar results were also observed in the subgroup of patients without 'bleeding' TIPS-indication, with improvements of G ≥ 2 thrombocytopenia and of G ≥ 2 anemia in 19.8% and 10.2% of patients after TIPS, respectively. CONCLUSIONS: Thrombocytopenia, anemia, and leukopenia frequently improved after TIPS. Therefore, moderate- to higher-grade thrombocytopenia should not be regarded as a contraindication against TIPS, but rather be considered in case of severe thrombocytopenia-particularly prior to surgery or interventions.

Clinical Course of Porto-Sinusoidal Vascular Disease Is Distinct From Idiopathic Noncirrhotic Portal Hypertension.

BACKGROUND & AIMS: Porto-sinusoidal vascular disease (PSVD) was recently proposed as novel clinical entity characterized by typical histological changes with or without portal hypertension (PH) in the absence of cirrhosis. Thus, we aimed to describe clinical characteristics and the outcome of PSVD patients and to compare these to patients meeting traditional idiopathic non-cirrhotic portal hypertension (INCPH) criteria. METHODS: Patients undergoing liver biopsy (baseline) ±hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 2000-2019 were screened for PSVD and INCPH criteria. RESULTS: 91 patients were diagnosed with PSVD of which 28 (30.8%) also fulfilled INCPH criteria (INCPH+/PSVD+). Specific histological and specific clinical PH signs were found in 72 (79.1%) and 54 (59.3%) patients, respectively. INCPH+/PSVD+ showed higher Child-Pugh-scores (7±2 vs 6±1 points; P = .002) and a higher prevalence of decompensation (57.1% vs 28.6%; P = .009) than INCPH-/PSVD+ patients. Importantly, hepatic decompensation after three years (3Y) occurred in 11.2% of PSVD patients with specific clinical signs of PH, while no decompensation occurred in patients with only specific histological or with unspecific clinical/histological signs (P = .002). When categorizing by INCPH definition, 3Y decompensation was 13.4% in INCPH+/PSVD+ and 3.8% in INCPH-/PSVD+ (P = .120). While overall mortality was similar in INCPH+/PSVD+ (n = 6; 21.4%) and INCPH-/PSVD+ (n = 10; 15.9%) patients (P = .558), liver-related mortality tended to be higher in INCPH+/PSVD+ (6.9%) than in INCPH-/PSVD+ (0%; P = .078). CONCLUSION: Novel PSVD criteria facilitate diagnosis. Compared to INCPH, clinical course of PSVD patients is more favorable. Importantly, specific signs of PH including varices and collaterals are associated with hepatic decompensation and mortality.

Distinct structural and dynamic components of portal hypertension in different animal models and human liver disease etiologies.

BACKGROUND AND AIMS: Liver fibrosis is the static and main (70%-80%) component of portal hypertension (PH). We investigated dynamic components of PH by a three-dimensional analysis based on correlation of hepatic collagen proportionate area (CPA) with portal pressure (PP) in animals or HVPG in patients. APPROACH AND RESULTS: Different animal models (bile duct ligation: n = 31, carbon tetrachloride: n = 12, thioacetamide: n = 12, choline-deficient high-fat diet: n = 12) and patients with a confirmed single etiology of cholestatic (primary biliary cholangitis/primary sclerosing cholangitis: n = 16), alcohol-associated (n = 22), and metabolic (NASH: n = 19) liver disease underwent CPA quantification on liver specimens/biopsies. Based on CPA-to-PP/HVPG correlation, potential dynamic components were identified in subgroups of animals/patients with lower-than-expected and higher-than-expected PP/HVPG. Dynamic PH components were validated in a patient cohort (n = 245) using liver stiffness measurement (LSM) instead of CPA. CPA significantly correlated with PP in animal models (Rho = 0.531; p < 0.001) and HVPG in patients (Rho = 0.439; p < 0.001). Correlation of CPA with PP/HVPG varied across different animal models and etiologies in patients. In models, severity of hyperdynamic circulation and specific fibrosis pattern (portal fibrosis: p = 0.02; septa width: p = 0.03) were associated with PH severity. In patients, hyperdynamic circulation (p = 0.04), vascular dysfunction/angiogenesis (VWF-Ag: p = 0.03; soluble vascular endothelial growth factor receptor 1: p = 0.03), and bile acids (p = 0.04) were dynamic modulators of PH. The LSM-HVPG validation cohort confirmed these and also indicated IL-6 (p = 0.008) and hyaluronic acid (HA: p < 0.001) as dynamic PH components. CONCLUSIONS: The relative contribution of "static" fibrosis on PH severity varies by type of liver injury. Next to hyperdynamic circulation, increased bile acids, VWF-Ag, IL-6, and HA seem to indicate a pronounced dynamic component of PH in patients.

Prognostic impact of sarcopenia in cirrhotic patients stratified by different severity of portal hypertension.

BACKGROUND AND AIMS: Portal hypertension (PH) and sarcopenia are common in patients with advanced chronic liver disease (ACLD). However, the interaction between PH and sarcopenia and their specific and independent impact on prognosis and mortality has yet to be systematically investigated in patients with ACLD. METHODS: Consecutive patients with ACLD and hepatic venous pressure gradient (HVPG) ≥10 mm Hg with available CT/MRI imaging were included. Sarcopenia was defined by transversal psoas muscle thickness (TPMT) at <12 mm/m in men and <8 mm/m in women at the level of the third lumbar vertebrae. Hepatic decompensation and mortality was recorded during follow-up. RESULTS: Among 203 patients (68% male, age: 55 ± 11, model for end-stage liver disease [MELD]: 12 [9-15]), sarcopenia was observed in 77 (37.9%) and HVPG was ≥20 mm Hg in 98 (48.3%). There was no correlation between TPMT and HVPG (r = .031, P = .66), median HVPG was not different between patients with vs without sarcopenia (P = .211). Sarcopenia was significantly associated with first/further decompensation both in compensated (SHR: 3.05, P = .041) and in decompensated patients (SHR: 1.86, P = .021). Furthermore, sarcopenia (SARC) was a significant predictor of mortality irrespective of HVPG (HVPG < 20-SARC: SHR: 2.25, P = .021; HVPG ≥ 20-SARC: SHR: 3.33, P = .001). On multivariate analysis adjusted for age, HVPG and MELD, sarcopenia was an independent risk factor for mortality (aHR: 1.99, 95% confidence interval: 1.2-3.3, P = .007). CONCLUSION: Sarcopenia has a major impact on clinical outcomes both in compensated and in decompensated ACLD patients. The presence of sarcopenia doubled the risk for mortality independently from the severity of PH.

Placental growth factor levels neither reflect severity of portal hypertension nor portal-hypertensive gastropathy in patients with advanced chronic liver disease.

BACKGROUND & AIMS: Experimental data indicates that placental growth factor (PLGF) is involved in the pathophysiology of portal hypertension (PH) due to advanced chronic liver disease (ACLD). We investigated serum levels of PLGF and its "scavenger", the receptor soluble fms-like tyrosine kinase-1 (sFLT1, or sVEGFR1), in ACLD patients with different severity of PH and portal-hypertensive gastropathy (PHG). METHODS: PLGF and sVEGFR1 were measured in ACLD patients with hepatic venous pressure gradient (HVPG) ≥6 mmHg (n = 241) and endoscopic evaluation of PHG (n = 216). Patients with pre-/posthepatic PH, TIPS, liver transplantation and hepatocellular carcinoma were excluded. RESULTS: Thirty-two (13%) patients had HVPG 6-9 mmHg, 128 (53%) 10-19 mmHg and 81 (34%) ≥20 mmHg; 141 (59%) had decompensated ACLD (dACLD). PLGF (median 17.2 vs. 20.8 vs. 22.4 pg/mL; p = 0.002), sVEGFR1 (median 96.0 vs. 104.8 vs. 119.3 pg/mL; p < 0.001) levels increased across HVPG strata, while PLGF/sVEGFR1 ratios remained similar (0.19 vs. 0.20 vs. 0.18 pg/mL; p = 0.140). The correlation between PLGF and HVPG was weak (Rho = 0.190,95%CI 0.06-0.31; p = 0.003), and the PLGF/sVEGFR1 ratio did not correlate with HVPG (p = 0.331). The area-under-the-receiver operating characteristics (AUROC) for PLGF to detect clinically significant PH (CSPH;i.e. HVPG ≥ 10 mmHg) yielded only 0.688 (0.60-0.78; p < 0.001). When compared to ACLD patients without PHG, PLGF levels (20 without vs. 21.4 with mild vs. 17.1 pg/mL with severe PHG, respectively; p = 0.005) and PLGF/sVEGFR1 ratios (0.20 vs. 0.19 vs. 0.17; p = 0.076) did not increase with mild and severe PHG. CONCLUSION: While PLGF levels tended to increase with severity of PH, the PLGF/sVEGFR1 ratio remained stable across HVPG strata. Neither PLGF nor the PLGF/sVEGFR1 ratio had diagnostic value for prediction of CSPH. The severity of PHG was also not associated with stepwise increases in PLGF levels or PLGF/sVEGFR1 ratio.

Magnetic Resonance Imaging for Evaluation of Interstitial Fibrosis in Kidney Allografts.

Interstitial fibrosis (IF) is the common pathway of chronic kidney injury in various conditions. Magnetic resonance imaging (MRI) may be a promising tool for the noninvasive assessment of IF in renal allografts. METHODS: This prospective trial was primarily designed to investigate whether the results of T1-weighted MRI associate with the degree of IF. Thirty-two kidney transplant recipients were subjected to 1.5-Tesla MRI scans shortly before or after routine allograft biopsies. MRI parameters [T1 and T2 relaxation times; apparent diffusion coefficient (ADC)] were assessed for cortical and medullary sections. RESULTS: Advanced IF (Banff ci score >1) was associated with higher cortical T1 (but not T2) values [1451 (median; interquartile range: 1331-1506) versus 1306 (1197-1321) ms in subjects with ci scores ≤1; P = 0.011; receiver operating characteristic area under the curve for prediction of ci > 1: 0.76]. In parallel, T1 values were associated with kidney function and proteinuria. There was also a relationship between IF and corticomedullary differences on ADC maps (receiver operating characteristic area under the curve for prediction of ci ≤ 1: 0.79). CONCLUSIONS: Our results support the use of MRI for noninvasive assessment of allograft scarring. Future studies will have to clarify the role of T1 (and ADC) mapping as a surrogate endpoint reflecting the progression of chronic graft damage.

Interdependence of VA-ECMO output, pulmonary congestion and outcome after cardiac surgery.

BACKGROUND: Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is a life-saving method for patients with low-output failure after cardiac surgery. However, VA-ECMO therapy may increase left ventricular afterload due to retrograde blood flow in the aorta, which may lead to progression of pulmonary congestion. We examined the predictive value of pulmonary congestion in patients that need VA-ECMO support after cardiovascular surgery. METHODS: We enrolled a total of 266 adult patients undergoing VA-ECMO support following cardiovascular surgery at a university-affiliated tertiary care centre into our single-center registry. Pulmonary edema was assessed on bedside chest X rays at day 0, 3, 5 after VA-ECMO implantation. RESULTS: Median age was 65 (57-72) years, 69% of patients were male and 30-day survival was 63%. At ICU-admission 20% of patients had mild, 54% had moderate and 26% showed severe pulmonary congestion. Pulmonary congestion at day 0 was not associated with outcome (adjusted HR 1.31; 95%-CI 0.89-1.93;P = 0.18), whereas pulmonary congestion at day 3 (adj. HR 2.81; 95%-CI 1.76-4.46;P<0.001) and day 5 (adj. HR 3.01;95%-CI 1.84-4.93;P<0.001) was significantly associated with survival. Linear regression revealed that out of left ventricular function, cardiac output, central venous saturation, maximum dobutamine and norepinephrine dose as well as fluid balance solely ECMO rotation was associated with the evolution of pulmonary congestion (P = 0.007). CONCLUSIONS: Pulmonary edema three and five days after ECMO implantation are associated with poor survival. Interestingly, a high VA-ECMO output was the most important determinant of worsening pulmonary congestion within the first five days.

MRI-defined sarcopenia predicts mortality in patients with chronic liver disease.

BACKGROUND & AIMS: To explore whether sarcopenia, diagnosed by an abbreviated magnetic resonance imaging (MRI) protocol is a risk factor for hepatic decompensation and mortality in patients with chronic liver disease (CLD). METHODS: In this retrospective single-centre study we included 265 patients (164 men, mean age 54 ± 16 years) with CLD who had undergone MRI of the liver between 2010 and 2015. Transverse psoas muscle thickness (TPMT) was measured on unenhanced and contrast-enhanced T1-weighted and T2-weighted axial images. Sarcopenia was defined by height-adjusted and gender-specific cut-offs in women as TPMT < 8 mm/m and in men as TPMT < 12 mm/m respectively. Patients were further stratified into three prognostic stages according to the absence of advanced fibrosis (FIB-4 < 1.45, non-advanced CLD), compensated-advanced CLD (cACLD) and decompensated-advanced CLD (dACLD). RESULTS: The inter-observer agreement for the TPMT measurements (κ = 0.98; 95% confidence interval [95% CI]:0.96-0.98), as well as the intra-observer agreement between the three image sequences (κ = 0.99; 95% CI: 0.99-1.00) were excellent. Sarcopenia was not predictive of first or further hepatic decompensation. In patients with cACLD and dACLD, sarcopenia was a risk factor for mortality (cACLD: hazard ratio (HR):3.13, 95% CI: 1.33-7.41, P = .009; dACLD:HR:2.45, 95% CI: 1.32-4.57, P = .005) on univariate analysis. After adjusting for the model of end-stage liver disease (MELD) score, albumin and evidence of clinical significant portal hypertension, sarcopenia (adjusted HR: 2.76, 95% CI: 1.02-7.42, P = .045) remained an independent risk factor for mortality in patients with cACLD. CONCLUSION: Sarcopenia can be easily evaluated by a short MRI exam without the need for contrast injection. Sarcopenia is a risk factor for mortality, especially in patients with cACLD.

Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis.

BACKGROUND & AIMS: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis. METHODS: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint. RESULTS: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02-2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA. CONCLUSION: This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis. LAY SUMMARY: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.

The value of different CT-based methods for diagnosing low muscle mass and predicting mortality in patients with cirrhosis.

BACKGROUND & AIMS: Low muscle mass impacts on morbidity and mortality in cirrhosis. The skeletal-muscle index (SMI) is a well-validated tool to diagnose muscle wasting, but requires specialized radiologic software and expertise. Thus, we compared different Computed tomography (CT)-based evaluation methods for muscle wasting and their prognostic value in cirrhosis. METHODS: Consecutive cirrhotic patients included in a prospective registry undergoing abdominal CT scans were analysed. SMI, transversal psoas muscle thickness (TPMT), total psoas volume (TPV) and paraspinal muscle index (PSMI) were measured. Sarcopenia was defined using SMI as a reference method by applying sex-specific cut-offs (males: <52.4 cm2 /m2 ; females: <38.5 cm2 /m2 ). RESULTS: One hundred and nine patients (71.6% male) of age 57 ± 11 years, MELD 16 (8-26) and alcoholic liver disease (63.3%) as the main aetiology were included. According to established SMI cut-offs, low muscle mass was present in 69 patients (63.3%) who also presented with higher MELD (17 vs 14 points; P = .025). The following optimal sex-specific cut-offs (men/women) for diagnosing low muscle mass were determined: TPMT: <10.7/ <7.8 mm/m, TPV: <194.9/ <99.2 cm3 and PSMI <26.3/ <20.8 cm2 /m2 . Thirty (27.5%) patients died during a follow-up of 15 (0.3-45.7) months. Univariate competing risks analyses showed a significant risk for mortality according to SMI (aSHR:2.52, 95% CI: 1.03-6.21, P = .043), TPMT (aSHR: 3.87, 95% CI: 1.4-8.09, P = .007) and PSMI (aSHR: 2.7, 95% CI: 1.17-6.23, P = .02), but not TPV (P = .18) derived low muscle mass cut-offs. In multivariate analysis only TPMT (aSHR: 2.82, 95% CI: 1.20-6.67, P = .018) was associated with mortality, SMI (aSHR: 1.93, 95% CI: 0.72-5.16, P = .19) and PSMI (aSHR: 1.93, 95% CI: 0.79-4.75, P = .15) were not. CONCLUSION: Low muscle mass was highly prevalent in our cohort of patients with cirrhosis. Gender-specific TPMT, SMI and PSMI cut-offs for low muscle mass can help identify patients with an increased risk for mortality. Importantly, only TPMT emerged as an independent risk factor for mortality in patients with cirrhosis.

Dysbalanced sex hormone status is an independent predictor of decompensation and mortality in patients with liver cirrhosis.

AIMS: Endocrinological abnormalities, including low testosterone levels, are prevalent in cirrhosis. We assessed sexual hormone status in regard to hemodynamic abnormalities and its impact on hepatic decompensation and survival. METHODS: Males with cirrhosis were prospectively included in this study since 2010. Sexual hormones including bioavailable testosterone, total testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex hormone-binding globulin as well as Child-Pugh score, Model for End-stage Liver Disease (MELD) score, and hepatic venous pressure gradient were recorded. Sarcopenia was also assessed in patients with available computed tomography scans. Clinical follow-up for hepatic decompensation, liver transplantation, and death was recorded until May 2017. RESULTS: One hundred fourteen male cirrhotic patients were included: age 55 ± 9.4 years, MELD 13.5 (range, 7-20.7). Etiologies were alcoholic liver disease in 61(53.5%) patients, viral in 30 (26.3%) patients, and other in 23 (20.2%). Child-Pugh scores were A in 32 (28.1%) patients, B in 48 (42.1%), and C in 34 (29.8%). Levels of bioavailable testosterone and total testosterone decreased with advanced Child-Pugh score (P < 0.001 and P < 0.001) whereas prolactin increased (P = 0.002). Median bioavailable testosterone (0.8 ng/mL [0.1-2] vs. 1.68 ng/mL [0.07-2.65]; P = 0.004) and total testosterone (2.7 ng/mL [0.23-12.34] vs. 7 ng/mL [0.25-10]; P = 0.041) levels were lower in patients with severe portal hypertension (hepatic venous pressure gradient >12 mmHg). Median bioavailable testosterone (0.25 ng/mL [0.07-1.7] vs. 0.97 ng/mL [0.15-2.74)]; P = 0.017) and total testosterone levels (1.28 ng/mL [0.25-7.32] vs. 4.32 ng/mL [0.43-13.47]; P = 0.031) were significantly lower in sarcopenic patients. Median follow-up was 13 months (0.2-75 months) and liver-related events were recorded in 46 patients (40.4%; death, 31 [27.2%]). Low total testosterone was associated with an increased risk for hepatic decompensation and/or death, even after adjusting for Child-Pugh score, MELD, and other relevant factors (Child-Pugh score model: hazard ratio 2.503, 95% confidence interval, 1.214-5.157, P = 0.013; MELD model: hazard ratio 3.065, 95% confidence interval, 1.523-6.169, P = 0.002). CONCLUSION: In parallel to increasing severity of cirrhosis, levels of testosterone decline whereas prolactin levels increase. However, low testosterone levels are independently associated with a higher risk for hepatic decompensation and mortality.

Anticoagulation in non-malignant portal vein thrombosis is safe and improves hepatic function.

BACKGROUND: Non-malignant portal vein thrombosis (PVT) is common in patients with advanced liver disease. Anticoagulation (AC) increases the chances of recanalization and may improve liver function in patients with cirrhosis. AIM: We retrospectively assessed the course of non-malignant PVT in patients receiving AC. METHODS: Parameters related to hepatic injury (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]), severity of disease (ascites) and synthesis function (albumin) as well as AC, rates of PVT regression/progression and AC-associated complications were documented. RESULTS: Among 122 patients with PVT, 51 patients with non-malignant PVT (27 incomplete, 24 complete) were included, 12 patients (25%) received long-term AC therapy (≥9 months) as compared to 36 patients without long-term AC. We observed a trend towards higher regression rates with long-term AC of 58% (vs. 28% without AC; p = 0.08) and lower progression rates of 25% (vs. 42% without AC; p = 0.15). In the subgroup of patients with decompensation prior to PVT diagnosis (n = 39), long-term AC (n = 10, 25.6%) resulted in a significantly higher rate of PVT regression/resolution (70% vs. 24%, p = 0.031). Interestingly, AST/ALT tended to decrease (-19%/-16%) and the proportion of patients with ascites became lower (-33%) with long-term AC (without AC: ±0%). Furthermore, there was a significant improvement in albumin levels (+9%/+3.6 g/dl) when compared to patients without long-term AC (-2%/-0.8 g/dl; p = 0.04). Additionally, 10 patients were treated with direct oral anticoagulants (DOACs) for splanchnic vein thrombosis. Importantly, there were no AC-associated bleeding events in patients with conventional AC and one bleeding event in patients with DOAC treatment (10%). CONCLUSION: Our findings support anticoagulation in patients with non-malignant PVT, since AC seems safe and associated with superior PVT regression rates and might also decrease hepatic injury and improve liver synthesis.