3D-Volumetric Shunt Measurement for Detection of High-Risk Esophageal Varices in Liver Cirrhosis.

Background and Objectives: Esophageal varices (EV) and variceal hemorrhages are major causes of mortality in liver cirrhosis patients. Detecting EVs early is crucial for effective management. Computed tomography (CT) scans, commonly performed for various liver-related indications, provide an opportunity for non-invasive EV assessment. However, previous CT studies focused on variceal diameter, neglecting the three-dimensional (3D) nature of varices and shunt vessels. This study aims to evaluate the potential of 3D volumetric shunt-vessel measurements from routine CT scans for detecting high-risk esophageal varices in portal hypertension. Methods: 3D volumetric measurements of esophageal varices were conducted using routine CT scans and compared to endoscopic variceal grading. Receiver operating characteristic (ROC) analyses were performed to determine the optimal cutoff value for identifying high-risk varices based on shunt volume. The study included 142 patients who underwent both esophagogastroduodenoscopy (EGD) and contrast-enhanced CT within six months. Results: The study established a cutoff value for identifying high-risk varices. The CT measurements exhibited a significant correlation with endoscopic EV grading (correlation coefficient r = 0.417, p < 0.001). A CT cutoff value of 2060 mm3 for variceal volume showed a sensitivity of 72.1% and a specificity of 65.5% for detecting high-risk varices during endoscopy. Conclusions: This study demonstrates the feasibility of opportunistically measuring variceal volumes from routine CT scans. CT volumetry for assessing EVs may have prognostic value, especially in cirrhosis patients who are not suitable candidates for endoscopy.

Association between endotoxemia and blood no in the portal circulation of cirrhotic patients: results of a pilot study.

Pathophysiology of portal vein thrombosis (PVT) in cirrhosis is still not entirely understood. Elevated levels of lipopolysaccharides (LPS) in portal circulation are significantly associated with hypercoagulation, increased platelet activation and endothelial dysfunction. The aim of the study was to investigate if LPS was associated with reduced portal venous flow, the third component of Virchow's triad, and the underlying mechanism. Serum nitrite/nitrate, as a marker of nitric oxide (NO) generation, and LPS were measured in the portal and systemic circulation of 20 patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedure; portal venous flow velocity (PVV) was also measured in each patient and correlated with NO and LPS levels. Serum nitrite/nitrate and LPS were significantly higher in the portal compared to systemic circulation; a significant correlation was found between LPS and serum nitrite/nitrate (R = 0.421; p < 0.01). Median PVV before and after TIPS was 15 cm/s (6-40) and 31 cm/s (14-79), respectively. Correlation analysis of PVV with NO and LPS showed a statistically significant negative correlation of PVV with portal venous NO concentration (R = - 0.576; p = 0.020), but not with LPS. In vitro study with endothelial cells showed that LPS enhanced endothelial NO biosynthesis, which was inhibited by L-NAME, an inhibitor of NO synthase, or TAK-242, an inhibitor of TLR4, the LPS receptor; this effect was accomplished by up-regulation of eNOS and iNOS. The study shows that in cirrhosis, endotoxemia may be responsible for reduced portal venous flow via overgeneration of NO and, therefore, contribute to the development of PVT.

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.

Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis.

Background & Aims: Although worsening liver-related symptoms during pregnancy can occur in primary sclerosing cholangitis (PSC), there are insufficient data to effectively counsel patients on their pre-conception risk and no clear recommendations on monitoring and management during pregnancy. We aimed to describe maternal liver-related symptoms in pregnancy, both before and after PSC diagnosis, and explore factors associated with worsening symptoms and liver-related outcomes. Methods: We conducted a multicentre retrospective observational study of females with PSC and known pregnancy with live birth, via the International PSC Study Group. We included 450 patients from 12 European centres. Data included clinical variables, liver-related symptoms (pruritus and/or cholangitis) during pregnancy, and liver biochemistry. A composite primary endpoint of transplant-free survival from time of PSC diagnosis was used. Results: There were 266 pregnancies in 178 patients following PSC diagnosis. Worsening liver-related symptoms were reported in 66/228 (28.9%) pregnancies; they had a reduced transplant-free survival (p = 0.03), which retained significance on multivariate analysis (hazard ratio 3.02, 95% CI 1.24-7.35; p = 0.02).Abnormal biochemistry and/or liver-related symptoms (pruritus and/or cholangitis) were noted during pregnancy before PSC diagnosis in 21/167 (12.6%) patients. They had a reduced transplant-free survival from pregnancy (p = 0.01), which did not retain significance in a multivariable model (hazard ratio 1.10, 95% CI 0.43-2.85; p = 0.84). Conclusions: Liver-related symptoms are frequently encountered during pregnancies before the diagnosis of PSC, and pregnancy may expose the pre-clinical phase of PSC in some patients. Worsening liver-related symptoms were seen in a third of our cohort with known PSC during pregnancy; and this subgroup had a poorer prognosis, which may be related to more advanced liver disease at time of pregnancy and/or a more severe disease phenotype. Impact and implications: Patients with PSC can develop worsening of their liver-related symptoms during pregnancy; however, risk factors for this and the long-term implications are not known. We identified that there is a significant risk of these symptoms in pregnancy, both before and after PSC has been diagnosed, particularly in patients with elevated alkaline phosphatase. Furthermore, our findings suggest that worsening symptoms during pregnancy may be associated with adverse long-term clinical outcomes of liver transplantation and death in patients with known PSC. This may be related to the presence of more advanced liver disease at time of pregnancy. This information can be used to counsel patients with PSC before conception and identify patients who need close follow-up after delivery.

Myosteatosis independently predicts transplant-free survival in patients with primary sclerosing cholangitis.

BACKGROUND: Primary Sclerosing Cholangitis (PSC) is a progressive cholestatic liver disease with liver transplantation (LT) as the only curative therapy. Some regions use body-weight-loss as standard-exception criteria for organ allocation but data on the impact of body composition on survival of patients with PSC is scarce. METHODS: Abdominal MRI of PSC patients were quantitatively analyzed for intramuscular fat fraction (IMFF) as surrogate of myosteatosis. Clinical and laboratory data were retrieved from patient records. Primary outcome was transplant-free survival (TFS). RESULTS: 116 PSC patients were included. Median age was 38 (18-71) years with 74 (64%) male patients. 15 (13%) patients had significant weigh loss. IMFF was significantly associated with survival. Multivariate regression analysis showed IMFF ≥ 15% as independent predictor for TFS (p = 0.032, HR 3.215 CI 1.104-9.366), but not significant weight loss (p = 0.618). CONCLUSION: IMFF is independently associated with TFS in patients with PSC and may identify patients with more urgent need for LT. NCT03584204.

Maternal and Perinatal Outcome in a Contemporary Cohort of Patients with Portal Hypertension: A Single-Center Experience.

BACKGROUND: Portal hypertension in pregnancy is characterized by an increased perinatal and maternal complication rate. The purpose of this study was to evaluate the perinatal and maternal outcomes of these high-risk pregnancies at our tertiary center. METHODS: We identified pregnancies with portal hypertension in our departmental database for the years 2013 to 2021. The medical history and perinatal and maternal data were extracted from medical records. RESULTS: Eleven cases were identified. In pregnancy, delivery and postpartum, complications occurred in 72.7% of cases and included among others ascites, subclavian thrombosis, variceal-ligation-induced ulcer bleeding and postoperative hemorrhage. The cesarean delivery rate was 72.7% (n = 8); five of these were done for obstetric or fetal indications. The rate of preterm birth and admissions to neonatal intensive care unit were high (54.5% and 45.5%, respectively). CONCLUSIONS: Our case series substantiates the high maternal and perinatal complication rates seen in portal hypertension. The prevention of thromboembolic and bleeding complications was the main challenge. Care by an interdisciplinary team of experts is crucial for a successful perinatal and maternal outcome.

Surgical site infections are independently associated with the development of postoperative acute-on-chronic liver failure in liver cirrhosis.

Acute-on-chronic liver failure (ACLF) is associated with organ failure and high short-term mortality. Bacterial infections and surgery have been reported as major precipitants for ACLF. However, detailed characterization of postoperative infections after elective surgery in patients with liver cirrhosis and their impact on the development of ACLF have not been investigated yet. A total of 235 patients with cirrhosis without ACLF and proven bacterial infections undergoing elective surgery were included. The primary end point was the development of ACLF within 28 days after surgery, and secondary end points were infection development within 28 days and 3-month ACLF-related mortality. Cox regression analysis was used for identification of risk factors associated with ACLF development, infection development, and mortality. A total of 86 patients (37%) developed ACLF within 28 days after surgery. Patients with new postoperative infections had significantly higher rates of associated ACLF episodes within 28 days (51% vs. 24%, p < 0.001) and higher 3-month mortality ( p < 0.05) than patients without postoperative infections. New infections after surgery [HR: 2.43 (1.59-3.71), p < 0.001] and organ/space surgical site infections [HR: 2.46 (1.26-4.80), p = 0.01] in particular were independent risk factors associated with ACLF development 28 days after surgery. Extensive procedures were associated with the development of new postoperative infection episodes within 28 days. Infections treated with initial appropriate empirical antibiotic strategies showed significantly improved survival. This study characterizes and identifies bacterial infections in general and organ/space surgical site infection in particular as precipitating events for the development of ACLF after elective surgery in patients with cirrhosis. Postoperative ACLF combined with infections leads to higher postoperative short-term mortality than each condition separately, especially in extensive procedures. Interdisciplinary care, early identification of postoperative ACLF and infections, and adequate, broad, and early treatment strategies are needed to improve postoperative outcome.

Cardiac involvement in non-cirrhotic portal hypertension: MRI detects myocardial fibrosis and oedema similar to compensated cirrhosis.

AIMS: The exact role of portal hypertension in cirrhotic cardiomyopathy remains unclear, and it is uncertain whether cardiac abnormalities also occur in non-cirrhotic portal hypertension (NCPH). This magnetic resonance imaging (MRI) study aimed to evaluate the presence of subclinical myocardial dysfunction, oedema, and fibrosis in NCPH. METHODS AND RESULTS: In this prospective study (2018-2022), participants underwent multiparametric abdominal and cardiac MRI including assessment of cardiac function, myocardial oedema, late gadolinium enhancement (LGE), and abdominal and cardiac mapping [T1 and T2 relaxation times, extracellular volume fraction (ECV)]. A total of 111 participants were included [44 participants with NCPH (48 ± 15 years; 23 women), 47 cirrhotic controls, and 20 healthy controls]. The cirrhotic group was dichotomized (Child A vs. Child B/C). NCPH participants demonstrated a more hyperdynamic circulation compared with healthy controls (cardiac index: 3.7 ± 0.6 vs. 3.2 ± 0.8 L/min/m², P = 0.004; global longitudinal strain: -27.3 ± 4.6 vs. -24.6 ± 3.5%, P = 0.022). The extent of abnormalities indicating myocardial fibrosis and oedema in NCPH was comparable with Child A cirrhosis (e.g. LGE presence: 32 vs. 33 vs. 69%, P = 0.004; combined T1 and T2 elevations: 46 vs. 27 vs. 69%, P = 0.017; NCPH vs. Child A vs. Child B/C). Correlations between splenic T1 and myocardial T1 values were found (r = 0.41; P = 0.007). Splenic T1 values were associated with the presence of LGE (odds ratio, 1.010; 95% CI: 1.002, 1.019; P = 0.013). CONCLUSION: MRI parameters of myocardial fibrosis and oedema were altered in participants with NCPH to a similar extent as in compensated cirrhosis and were associated with splenic markers of portal hypertension, indicating specific portal hypertensive cardiomyopathy.

Targeted decrease of portal hepatic pressure gradient improves ascites control after TIPS.

BACKGROUND: Ascites is a definitive sign of decompensated liver cirrhosis driven by portal hypertension. Although transjugular intrahepatic portosystemic shunt insertion (TIPS) is indicated for therapy of recurrent and refractory ascites, there is no evidence-based recommendation for a specific target of portal hepatic pressure gradient (PPG) decrease. METHODS: In this single-center, retrospective trial, we investigated the decrease of PPG in 341 patients undergoing TIPS insertion for therapy of refractory or recurrent ascites until 2015. During each procedure, portal and inferior vena cava pressures were invasively measured and correlated with patients' outcome and ascites progression over time, according to the prespecified Noninvasive Evaluation Program for TIPS and Follow-Up Network protocol (NCT03628807). RESULTS: Patients without ascites at 6 weeks after TIPS had significantly greater PPG reduction immediately after TIPS, compared to the patients with refractory ascites (median reduction 65% vs. 55% of pre-TIPS PPG; p = 0.001). Survival was significantly better if ascites was controlled, compared to patients with need for paracentesis 6 weeks after TIPS (median survival: 185 vs. 41 weeks; HR 2.0 [1.3-2.9]; p < 0.001). Therefore, higher PPG reduction by TIPS ( p = 0.005) and lower PPG after TIPS ( p = 0.02) correlated with resolution of severe ascites 6 weeks after TIPS. Multivariable analyses demonstrated that higher Child-Pugh score before TIPS (OR 1.3 [1.0-1.7]; p = 0.03) and lower serum sodium levels (OR 0.9 [0.9-1.0]; p = 0.004) were independently associated with ascites persistence 6 weeks after TIPS, whereas PPG reduction (OR 0.98 [0.97-1.00]; p = 0.02) was associated with resolution of ascites 6 weeks after TIPS. CONCLUSION: Extent of PPG reduction and/or lowering of target PPG immediately after TIPS placement is associated with improved ascites control in the short term and with survival in the long term. A structured follow-up visit for patients should assess persistence of ascites at 6 weeks after TIPS.

Assessment of liver cirrhosis severity with extracellular volume fraction MRI.

We aimed to investigate the diagnostic utility of MRI extracellular volume fraction (ECV) for the assessment of liver cirrhosis severity as defined by Child-Pugh class. In this retrospective study, 90 patients (68 cirrhotic patients and 22 controls), who underwent multiparametric liver MRI, were identified. Hepatic T1 relaxation times and ECV were assessed. Clinical scores of liver disease severity were calculated. One-way analysis of variance (ANOVA) followed by Tukey's multiple comparison test, Spearman's correlation coefficient, and receiver operating characteristic (ROC) analysis were used for statistical analysis. In cirrhotic patients, hepatic native T1 increased depending on Child-Pugh class (620.5 ± 78.9 ms (Child A) vs. 666.6 ± 73.4 ms (Child B) vs. 828.4 ± 91.2 ms (Child C), P < 0.001). ECV was higher in cirrhotic patients compared to the controls (40.1 ± 11.9% vs. 25.9 ± 4.5%, P < 0.001) and increased depending of Child-Pugh class (33.3 ± 6.0% (Child A) vs. 39.6 ± 4.9% (Child B) vs. 52.8 ± 1.2% (Child C), P < 0.001). ECV correlated with Child-Pugh score (r = 0.64, P < 0.001). ECV allowed differentiating between Child-Pugh classes A and B, and B and C with an AUC of 0.785 and 0.944 (P < 0.001, respectively). The diagnostic performance of ECV for differentiating between Child-Pugh classes A and B, and B and C was higher compared to hepatic native T1 (AUC: 0.651 and 0.910) and MELD score (AUC: 0.740 and 0.795) (P < 0.05, respectively). MRI-derived ECV correlated with Child-Pugh score and had a high diagnostic performance for the discrimination of different Child-Pugh classes. ECV might become a valuable non-invasive biomarker for the assessment of liver cirrhosis severity.

Combination of Fat-Free Muscle Index and Total Spontaneous Portosystemic Shunt Area Identifies High-Risk Cirrhosis Patients.

Background: Sarcopenia and spontaneous portosystemic shunts (SPSSs) are common complications of liver cirrhosis, and both are associated with higher rates of hepatic encephalopathy (HE) development in these patients. This study aimed to evaluate the simultaneous impact of skeletal muscle mass and spontaneous portosystemic shunting, measured from routine diagnostic CT on outcomes in patients with liver cirrhosis. Methods: Retrospective analysis of patients with cirrhosis. Skeletal muscle mass [including fat-free muscle index (FFMI) as a surrogate for sarcopenia] and total cross-sectional spontaneous portosystemic shunt area (TSA) were quantified from CT scans. The primary endpoint was the development of HE, while the secondary endpoint was 1-year mortality. Results: One hundred fifty-six patients with liver cirrhosis were included. Patients with low (L-) FFMI and large (L-)TSA showed higher rates of HE development. In multivariable analysis, L-FFMI and L-TSA were independent predictors of HE development (L-FFMI HR = 2.69, CI 1.22-5.93; L-TSA, HR = 2.50, CI = 1.24-4.72) and 1-year mortality (L-FFMI, HR = 7.68, CI 1.75-33.74; L-TSA, HR = 3.05, CI 1.32-7.04). The simultaneous presence of L-FFMI and L-TSA exponentially increased the risk of HE development (HR 12.79, CI 2.93-55.86) and 1-year mortality (HR 13.66, CI 1.75-106.50). An easy sequential algorithm including FFMI and TSA identified patients with good, intermediate, and poor prognoses. Conclusion: This study indicates synergy between low skeletal muscle mass and large TSA to predict exponentially increased risk of HE development and mortality in liver cirrhosis. Simultaneous screening for sarcopenia and TSA from routine diagnostic CT may help to improve the identification of high-risk patients using an easy-to-apply algorithm. Clinical Trial registration: [ClinicalTrials.gov], identifier [NCT03584204].

Deep learning supports the differentiation of alcoholic and other-than-alcoholic cirrhosis based on MRI.

Although CT and MRI are standard procedures in cirrhosis diagnosis, differentiation of etiology based on imaging is not established. This proof-of-concept study explores the potential of deep learning (DL) to support imaging-based differentiation of the etiology of liver cirrhosis. This retrospective, monocentric study included 465 patients with confirmed diagnosis of (a) alcoholic (n = 221) and (b) other-than-alcoholic (n = 244) cirrhosis. Standard T2-weighted single-slice images at the caudate lobe level were randomly split for training with fivefold cross-validation (85%) and testing (15%), balanced for (a) and (b). After automated upstream liver segmentation, two different ImageNet pre-trained convolutional neural network (CNN) architectures (ResNet50, DenseNet121) were evaluated for classification of alcohol-related versus non-alcohol-related cirrhosis. The highest classification performance on test data was observed for ResNet50 with unfrozen pre-trained parameters, yielding an area under the receiver operating characteristic curve of 0.82 (95% confidence interval (CI) 0.71-0.91) and an accuracy of 0.75 (95% CI 0.64-0.85). An ensemble of both models did not lead to significant improvement in classification performance. This proof-of-principle study shows that deep-learning classifiers have the potential to aid in discriminating liver cirrhosis etiology based on standard MRI.

Cranial stent position is independently associated with the development of TIPS dysfunction.

Complications of portal hypertension can be treated with transjugular intrahepatic portosystemic shunt (TIPS) in selected patients. TIPS dysfunction is a relevant clinical problem. This study investigated the prognostic value of two-dimensional (2D) TIPS geometry for the development of TIPS dysfunction. Three hundred and seven patients undergoing TIPS procedure between 2014 and 2019 were analyzed in this monocentric retrospective study. 2D angiograms from the patients with and without TIPS dysfunction were reviewed to determine geometric characteristics including insertion and curve angles and the location of the stent. Primary outcome was the development of TIPS dysfunction. A total of 70 patients developed TIPS dysfunction and were compared to the dysfunction-free (n = 237) patients. The position of the cranial stent end in the hepatic vein and the persistence of spontaneous portosystemic shunts were significantly associated with the development of TIPS dysfunction. Among significant parameters in univariable regression analysis (portal vein-pressure after TIPS, Child-Pugh Score before TIPS, MELD before TIPS and white blood cell count before TIPS), multivariable models showed cranial stent position (p = 0.027, HR 2.300, 95% CI 1.101-4.806) and SPSS embolization (p = 0.006, HR 0.319, 95% CI 0.140-0.725) as the only predictors of TIPS dysfunction. This monocentric study demonstrates that the position of the cranial stent end is independently associated with the development of TIPS dysfunction. The distance of the cranial stent end to the IVC at the time of TIPS placement should be less than 1 cm in 2D angiography.

Preoperative TIPS prevents the development of postoperative acute-on-chronic liver failure in patients with high CLIF-C AD score.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome associated with organ failure and high short-term mortality. Recently, the role of surgery as a precipitating event for ACLF has been characterised. However, the impact of preoperative transjugular intrahepatic portosystemic shunt (TIPS) placement on ACLF development in patients with cirrhosis undergoing surgery has not been investigated yet. METHODS: A total of 926 patients (363 with cirrhosis undergoing surgery and 563 patients with TIPS) were screened. Forty-five patients with preoperative TIPS (TIPS group) were 1:1 propensity matched to patients without preoperative TIPS (no-TIPS group). The primary endpoint was the development of ACLF within 28 and 90 days after surgery. The secondary endpoint was 1-year mortality. Results were confirmed by a differently 1:2 matched cohort (n = 176). RESULTS: Patients in the no-TIPS group had significantly higher rates of ACLF within 28 days (29 vs. 9%; p = 0.016) and 90 days (33 vs. 13%; p = 0.020) after surgery as well as significantly higher 1-year mortality (38 vs. 18%; p = 0.023) compared with those in the TIPS group. Surgery without preoperative TIPS and Chronic Liver Failure Consortium-Acute Decompensation (CLIF-C AD) score were independent predictors for 28- and 90-day ACLF development and 1-year mortality after surgery, especially in patients undergoing visceral surgery. In the no-TIPS group, a CLIF-C AD score of >45 could be identified as cut-off for patients at risk for postoperative ACLF development benefiting from TIPS. CONCLUSIONS: This study suggests that preoperative TIPS may result in lower rates of postoperative ACLF development especially in patients undergoing visceral surgery and with a CLIF-C AD score above 45. LAY SUMMARY: Acute-on-chronic liver failure (ACLF) is a syndrome that is associated with high short-term mortality. Surgical procedures are a known precipitating event for ACLF. This study investigates the role of preoperative insertion of a transjugular intrahepatic portosystemic shunt (TIPS) on postoperative mortality and ACLF development. Patients with TIPS insertion before a surgical procedure exhibit improved postoperative survival and lower rates of postoperative ACLF, especially in patients undergoing visceral surgery and with a high CLIF-C AD prognostic score. Thus, this study suggests preoperative TIPS insertion in those high-risk patients.

Model for end-stage liver disease underestimates mortality of patients with acute-on-chronic liver failure waiting for liver transplantation.

BACKGROUND AND AIMS: Patients with acute-on-chronic liver failure (ACLF) show excess mortality in MELD-Na based organ allocation for liver transplantation (LT). Whether MELD-based allocation in the Eurotransplant region similarly underprioritizes ACLF patients is unknown. METHODS: 428 patients listed for LT from 01/2010 to 02/2021 at a tertiary center in Germany were screened and 209 patients included as derivation (n = 123) and validation cohort (n = 86). Competing risk analysis for waitlist mortality and LT as competing events was performed. RESULTS: 90-day waitlist mortality for patients with MELD < and ≥ 25 at baseline was 9% vs. 33%, respectively (p = 0.009). Competing risk analysis shows significantly higher 90-day waitlist mortality in patients listed with ACLF compared to those without ACLF (p = 0.021) in the low MELD stratum. Probability of LT was similar between the two groups (p = 0.91). In the high MELD group, 90-day waitlist mortality and rates of LT were not significantly different between patients with and without ACLF (31% vs. 20%, p = 0.55 and 59% vs. 60%, p = 0.72, respectively). Post-transplant survival was similar between patients with and without ACLF. This result was confirmed in the validation cohort. CONCLUSION: MELD-based organ allocation in the Eurotransplant region underestimates waitlist mortality in patients with ACLF in lower MELD ranges.

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

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

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.

Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease.

OBJECTIVE: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients. DESIGN: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation. RESULTS: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM. CONCLUSION: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.

Extrahepatic Surgery in Cirrhosis Significantly Increases Portal Pressure in Preclinical Animal Models.

Background: Liver cirrhosis is a relevant comorbidity with increasing prevalence. Postoperative decompensation and development of complications in patients with cirrhosis remains a frequent clinical problem. Surgery has been discussed as a precipitating event for decompensation and complications of cirrhosis, but the underlying pathomechanisms are still obscure. The aim of this study was to analyze the role of abdominal extrahepatic surgery in cirrhosis on portal pressure and fibrosis in a preclinical model. Methods: Compensated liver cirrhosis was induced using tetrachlormethane (CCL4) inhalation and bile duct ligation (BDL) models in rats, non-cirrhotic portal hypertension by partial portal vein ligation (PPVL). Intestinal manipulation (IM) as a model of extrahepatic abdominal surgery was performed. 2 and 7 days after IM, portal pressure was measured in-vivo. Hydroxyproline measurements, Sirius Red staining and qPCR measurements of the liver were performed for evaluation of fibrosis development and hepatic inflammation. Laboratory parameters of liver function in serum were analyzed. Results: Portal pressure was significantly elevated 2 and 7 days after IM in both models of cirrhosis. In the non-cirrhotic model the trend was the same, while not statistically significant. In both cirrhotic models, IM shows strong effects of decompensation, with significant weight loss, elevation of liver enzymes and hypoalbuminemia. 7 days after IM in the BDL group, Sirius red staining and hydroxyproline levels showed significant progression of fibrosis and significantly elevated mRNA levels of hepatic inflammation compared to the respective control group. A progression of fibrosis was not observed in the CCL4 model. Conclusion: In animal models of cirrhosis with continuous liver injury (BDL), IM increases portal pressure, and development of fibrosis. Perioperative portal pressure and hence inflammation processes may be therapeutic targets to prevent post-operative decompensation in cirrhosis.