Performance of spleen stiffness measurement to rule out high-risk varices in patients with porto-sinusoidal vascular disorder.

BACKGROUND AIMS: Baveno VII consensus suggests that screening endoscopy can be spared in patients with compensated cirrhosis when spleen stiffness measurement (SSM) by vibration-controlled transient elastography (VCTE) is ≤40 kPa as they have a low probability of high-risk varices (HRV). Conversely, screening endoscopy is required in all patients with porto-sinusoidal vascular disorder (PSVD). This study aimed to evaluate the performance of SSM-VCTE to rule out HRV in patients with PSVD and signs of portal hypertension. APPROACH RESULTS: We retrospectively included patients with PSVD, ≥1 sign of portal hypertension, without history of variceal bleeding, who underwent a SSM-VCTE within 2 years before or after an upper endoscopy in 21 VALDIG centers, divided into a derivation and a validation cohort. 154 patients were included in the derivation cohort; 43% had HRV. By multivariable logistic regression analysis, SSM-VCTE >40 kPa and serum bilirubin ≥1 mg/dL were associated with HRV. SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL had a sensitivity of 96% to rule out HRV, and could spare 38% of screening endoscopies, with 4% of HRV missed, and a 95% negative predictive value (NPV). In the validation cohort, including 155 patients, SSM combined with bilirubin could spare 21% of screening endoscopies, with 4% of HRV missed and a 94% NPV. CONCLUSION: This study gathering a total of 309 PSVD patients showed that SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL identifies patients with PSVD and portal hypertension with a probability of HRV <5%, in whom screening endoscopy can be spared.

Episodic overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt does not increase mortality in patients with cirrhosis.

BACKGROUND & AIMS: Overt hepatic encephalopathy (OHE) is a major complication of transjugular intrahepatic portosystemic shunt (TIPS) placement, given its high incidence and possibility of refractoriness to medical treatment. Nevertheless, the impact of post-TIPS OHE on mortality has not been investigated in a large population. METHODS: We designed a multicenter, non-inferiority, observational study to evaluate the mortality rate at 30 months in patients with and without OHE after TIPS. We analyzed a database of 614 patients who underwent TIPS in three Italian centers and estimated the cumulative incidence of OHE and mortality with competitive risk analyses, setting the non-inferiority limit at 0.12. RESULTS: During a median follow-up of 30 months (IQR 12-30), 293 patients developed at least one episode of OHE. Twenty-seven (9.2%) of them experienced recurrent/persistent OHE. Patients with OHE were older (64 [57-71] vs. 59 [50-67] years, p <0.001), had lower albumin (3.1 [2.8-3.5] vs. 3.25 [2.9-3.6] g/dl, p = 0.023), and had a higher prevalence of pre-TIPS OHE (15.4% vs. 9.0%, p = 0.023). Child-Pugh and MELD scores were similar. The 30-month difference in mortality between patients with and without post-TIPS OHE was 0.03 (95% CI -0.042 to 0.102). Multivariable analysis showed that age (subdistribution hazard ratio 1.04, 95% CI 1.02-1.05, p <0.001) and MELD score (subdistribution hazard ratio 1.09, 95% CI 1.05-1.13, p <0.001), but not post-TIPS OHE, were associated with a higher mortality rate. Similar results were obtained when patients undergoing TIPS for variceal re-bleeding prophylaxis (n = 356) or refractory ascites (n = 258) were analyzed separately. The proportion of patients with persistent OHE after TIPS was significantly higher in the group of patients who died. The robustness of these results was increased following propensity score matching. CONCLUSION: Episodic OHE after TIPS is not associated with mortality in patients undergoing TIPS, regardless of the indication. IMPACT AND IMPLICATIONS: Overt hepatic encephalopathy (OHE) is a common complication in patients with advanced liver disease and it is particularly frequent following transjugular intrahepatic portosystemic shunt (TIPS) placement. In patients with cirrhosis outside the setting of TIPS, the development of OHE negatively impacts survival, regardless of the severity of cirrhosis or the presence of acute-on-chronic liver failure. In this multicenter, non-inferiority, observational study we demonstrated that post-TIPS OHE does not increase the risk of mortality in patients undergoing TIPS, irrespective of the indication. This finding alleviates concerns regarding the weight of this complication after TIPS. Intensive research to improve patient selection and risk stratification remains crucial to enhance the quality of life of patients and caregivers and to avoid undermining the positive effects of TIPS on survival.

Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis.

BACKGROUND & AIMS: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. METHODS: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. RESULTS: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes. CONCLUSIONS: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. IMPACT AND IMPLICATIONS: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis.

Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here we investigate the prognostic value of HVPG in compensated (cACLD) MASLD. METHODS: This European multicentre study included MASLD-cACLD patients characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest. RESULTS: 340 MASLD-cACLD patients [56.2% men; age: 62 (55-68) years; MELD: 8 (7-9); 71.2% diabetes] were included. Clinically significant portal hypertension (CSPH; i.e., HVPG ≥10 mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio, SHR:5.13; p<0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (aSHR per mmHg:1.12; p<0.001). Liver-related mortality occurred in 37 patients with a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (aSHR per mmHg:1.20; p<0.001). CONCLUSION: HVPG measurement is of high prognostic value in MASLD-cACLD. While MASLD-cACLD patients without CSPH show a very low short-term risk of decompensation and liver-related mortality is rare, the presence of CSPH substantially increases both risks. IMPACT AND IMPLICATIONS: While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in MASLD-cACLD patients without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk-stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD.

The role of transjugular intrahepatic portosystemic shunt in patients with cirrhosis and ascites: Recent evolution and open questions.

In selected patients with cirrhosis and ascites, transjugular intrahepatic portosystemic shunt (TIPS) placement improves control of ascites and may reduce mortality. In this review, we summarize the current knowledge concerning the use of TIPS for the treatment of ascites in patients with cirrhosis, from pathophysiology of ascites formation to hemodynamic consequences, patient selection, and technical issues of TIPS insertion. The combination of these factors is important to guide clinical decision-making and identify the best strategy for each individual patient. There is still a need to identify the best timing for TIPS placement in the natural history of ascites (recurrent vs. refractory) as well as which type and level of renal dysfunction is acceptable when TIPS is proposed for the treatment of ascites in cirrhosis. Future studies are needed to define the optimal stent diameter according to patient characteristics and individual risk of shunt-related side effects, particularly hepatic encephalopathy and insufficient cardiac response to hemodynamic consequences of TIPS insertion.

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.

Mortality after transjugular intrahepatic portosystemic shunt in older adult patients with cirrhosis: A validated prediction model.

BACKGROUND AND AIMS: Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) improves survival in patients with cirrhosis with refractory ascites and portal hypertensive bleeding. However, the indication for TIPS in older adult patients (greater than or equal to 70 years) is debated, and a specific prediction model developed in this particular setting is lacking. The aim of this study was to develop and validate a multivariable model for an accurate prediction of mortality in older adults. APPROACH AND RESULTS: We prospectively enrolled 411 consecutive patients observed at four referral centers with de novo TIPS implantation for refractory ascites or secondary prophylaxis of variceal bleeding (derivation cohort) and an external cohort of 415 patients with similar indications for TIPS (validation cohort). Older adult patients in the two cohorts were 99 and 76, respectively. A cause-specific Cox competing risks model was used to predict liver-related mortality, with orthotopic liver transplant and death for extrahepatic causes as competing events. Age, alcoholic etiology, creatinine levels, and international normalized ratio in the overall cohort, and creatinine and sodium levels in older adults were independent risk factors for liver-related death by multivariable analysis. CONCLUSIONS: After TIPS implantation, mortality is increased by aging, but TIPS placement should not be precluded in patients older than 70 years. In older adults, creatinine and sodium levels are useful predictors for decision making. Further efforts to update the prediction model with larger sample size are warranted.

5-MTHF enhances the portal pressure reduction achieved with propranolol in patients with cirrhosis: A randomized placebo-controlled trial.

BACKGROUND & AIMS: ß-blockers reduce hepatic venous pressure gradient (HVPG) by decreasing portal inflow, with no reduction in intrahepatic vascular resistance. 5-Methyltetrahydrofolate (5-MTHF) can prevent oxidative loss of tetrahydrobiopterin (BH4), a cofactor for endothelial nitric oxide synthase coupling. It also converts homocysteine (tHcy) into methionine and enables the degradation of asymmetric dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase. The aim of this study was to evaluate the effects of 5-MTHF in combination with propranolol on HVPG and nitric oxide bioavailability markers in patients with cirrhosis and portal hypertension. METHOD: Sixty patients with cirrhosis and HVPG ≥12 mmHg were randomized 1:1 to receive treatment with 5-MTHF+propranolol or placebo+propranolol for 90 days under double-blind conditions. HVPG and markers of nitric oxide bioavailability (BH4, ADMA and tHcy) were measured again at the end of treatment. RESULTS: Groups were similar in terms of baseline clinical and hemodynamic data and nitric oxide bioavailability markers. HVPG decreased in both groups, but the magnitude of the change was significantly greater in the group treated with 5-MTHF+propranolol compared to placebo+propranolol (percentage decrease, 20 [29-9] vs. 12.5 [22-0], p = 0.028), without differences in hepatic blood flow. At the end of treatment, 5-MTHF+propranolol (vs. placebo+propranolol) was associated with higher BH4 (1,101.4 ± 1,413.3 vs. 517.1 ± 242.8 pg/ml, p <0.001), lower ADMA (109.3 ± 52.7 vs. 139.9 ± 46.7 µmol/L, p = 0.027) and lower tHcy (µmol/L, 11.0 ± 4.6 vs. 15.4 ± 7.2 µmol/L, p = 0.010) plasma levels. CONCLUSION: In patients with cirrhosis and portal hypertension, 5-MTHF administration significantly enhanced the HVPG reduction achieved with propranolol. This effect appears to be mediated by improved nitric oxide bioavailability in the hepatic microcirculation. CLINICAL TRIAL EUDRACT NUMBER: 2014-002018-21. IMPACT AND IMPLICATIONS: Currently, the pharmacological prevention of cirrhosis complications due to portal hypertension, such as esophageal varices rupture, is based on the use of ß-blockers, but some patients still present with acute variceal bleeding, mainly due to an insufficient reduction of portal pressure. In this study, we sought to demonstrate that the addition of folic acid to ß-blockers is more effective in reducing portal pressure than ß-blockers alone. This finding could represent the basis for validation studies in larger cohorts, which could impact the future prophylactic management of variceal bleeding in cirrhosis. Enhancing the benefit of ß-blockers with a safe, accessible, cost-effective drug could improve clinical outcomes in cirrhosis, which in turn could translate into a reduction in the rates and costs of hospitalization, and ultimately into improved survival.

Assessment of portal hypertension severity using machine learning models in patients with compensated cirrhosis.

BACKGROUND & AIMS: In individuals with compensated advanced chronic liver disease (cACLD), the severity of portal hypertension (PH) determines the risk of decompensation. Invasive measurement of the hepatic venous pressure gradient (HVPG) is the diagnostic gold standard for PH. We evaluated the utility of machine learning models (MLMs) based on standard laboratory parameters to predict the severity of PH in individuals with cACLD. METHODS: A detailed laboratory workup of individuals with cACLD recruited from the Vienna cohort (NCT03267615) was utilised to predict clinically significant portal hypertension (CSPH, i.e., HVPG ≥10 mmHg) and severe PH (i.e., HVPG ≥16 mmHg). The MLMs were then evaluated in individual external datasets and optimised in the merged cohort. RESULTS: Among 1,232 participants with cACLD, the prevalence of CSPH/severe PH was similar in the Vienna (n = 163, 67.4%/35.0%) and validation (n = 1,069, 70.3%/34.7%) cohorts. The MLMs were based on 3 (3P: platelet count, bilirubin, international normalised ratio) or 5 (5P: +cholinesterase, +gamma-glutamyl transferase, +activated partial thromboplastin time replacing international normalised ratio) laboratory parameters. The MLMs performed robustly in the Vienna cohort. 5P-MLM had the best AUCs for CSPH (0.813) and severe PH (0.887) and compared favourably to liver stiffness measurement (AUC: 0.808). Their performance in external validation datasets was heterogeneous (AUCs: 0.589-0.887). Training on the merged cohort optimised model performance for CSPH (AUCs for 3P and 5P: 0.775 and 0.789, respectively) and severe PH (0.737 and 0.828, respectively). CONCLUSIONS: Internally trained MLMs reliably predicted PH severity in the Vienna cACLD cohort but exhibited heterogeneous results on external validation. The proposed 3P/5P online tool can reliably identify individuals with CSPH or severe PH, who are thus at risk of hepatic decompensation. IMPACT AND IMPLICATIONS: We used machine learning models based on widely available laboratory parameters to develop a non-invasive model to predict the severity of portal hypertension in individuals with compensated cirrhosis, who currently require invasive measurement of hepatic venous pressure gradient. We validated our findings in a large multicentre cohort of individuals with advanced chronic liver disease (cACLD) of any cause. Finally, we provide a readily available online calculator, based on 3 (platelet count, bilirubin, international normalised ratio) or 5 (platelet count, bilirubin, activated partial thromboplastin time, gamma-glutamyltransferase, choline-esterase) widely available laboratory parameters, that clinicians can use to predict the likelihood of their patients with cACLD having clinically significant or severe portal hypertension.

Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients.

BACKGROUND AND AIMS: People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. METHODS: We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). RESULTS: We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. CONCLUSIONS: Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone.

Endovascular Assessment of Liver Hemodynamics in Patients with Cirrhosis Complicated by Portal Hypertension.

The hepatic venous pressure gradient (HVPG) is currently considered the gold standard to assess portal hypertension (PH) in patients with cirrhosis. A meticulous technique is important to achieve accurate and reproducible results, and values obtained during measurement are applied in risk stratification of patients with PH, allocating treatment options, monitoring follow-up, and deciding management options in surgical patients. The use of portosystemic pressure gradients in patients undergoing placement of transjugular intrahepatic portosystemic shunts has been studied extensively and has great influence on decisions on shunt diameter. The purpose of this study was to describe the recommended technique to measure HVPG and portosystemic pressure gradient and to review the existing literature describing the importance of these hemodynamic measurements in clinical practice.

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.

Portosystemic shunt is an effective treatment for complications of portal hypertension in hepatic myeloid metaplasia and improves nutritional status.

In patients affected by myelofibrosis with hepatic myeloid metaplasia (HMM), portal hypertension (PHT) complications may develop. In this case series, we analysed the efficacy and safety of transjugular portosystemic shunt (TIPS) in the treatment of PHT-related complications and its effects on the nutritional status. Six patients were evaluated and the average follow-up period after TIPS was 33 (IQR 5) months. None of the patients developed hepatic failure, nor any recurrence of variceal bleeding was recorded. No additional paracentesis or endoscopic prophylactic treatment for PHT-related complications were required. In all subjects, the average dose of diuretics was almost halved three months after TIPS. Three patients died during the follow-up, but none for liver-related causes. All patients showed an improvement in the global nutritional status. In conclusion, TIPS represent an effective and safe treatment option for patients affected by complications of PHT secondary to HMM and drives to an improvement of the nutritional status.

Quality of life in liver transplant recipients during the Corona virus disease 19 pandemic: A multicentre study.

BACKGROUND: Liver transplant recipients require specific clinical and psychosocial attention given their frailty. Main aim of the study was to assess the quality of life after liver transplant during the current pandemic. METHODS: This multicentre study was conducted in clinically stable, liver transplanted patients. Enrollment opened in June and finished in September 2021. Patients completed a survey including lifestyle data, quality of life (Short Form health survey), sport, employment, diet. To examine the correlations, we calculated Pearson coefficients while to compare subgroups, independent samples t-tests and ANOVAs. To detect the predictors of impaired quality of life, we used multivariable logistic regression analysis. RESULTS: We analysed data from 511 patients observing significant associations between quality of life's physical score and both age and adherence to Mediterranean diet (p < .01). A significant negative correlation was observed between mental score and the sedentary activity (p < .05). Female patients scored significantly lower than males in physical and mental score. At multivariate analysis, females were 1.65 times more likely to report impaired physical score than males. Occupation and physical activity presented significant positive relation with quality of life. Adherence to Mediterranean diet was another relevant predictor. Regarding mental score, female patients were 1.78 times more likely to show impaired mental score in comparison with males. Sedentary activity and adherence to Mediterranean diet were further noteworthy predictors. CONCLUSIONS: Females and subjects with sedentary lifestyle or work inactive seem to show the worst quality of life and both physical activity and Mediterranean diet might be helpful to improve it.

Predictors of solid extra-hepatic non-skin cancer in liver transplant recipients and analysis of survival: A long-term follow-up study.

INTRODUCTION AND OBJECTIVES: De novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome. PATIENTS: We examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival. RESULTS: We analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n = 47) more often developed post-LT diabetes mellitus (DM) (57.4% versus 35,9%, p = 0.004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p = 0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p = 0.023). CONCLUSIONS: Post-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.

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

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

Relevance of Spontaneous Portosystemic Shunts Detected with CT in Patients with Cirrhosis.

Background Cirrhosis leads to portal hypertension and to the consequent formation of spontaneous portosystemic shunts (SPSSs), leading to complications related to the diversion of portal blood into the systemic circulation, which is called portosystemic shunt syndrome. Purpose To investigate the characteristics of patients with cirrhosis and an SPSS and secondarily to assess the prognostic impact of SPSSs on portal hypertension-related complications and transplant-free survival. Materials and Methods A retrospective database review of patients with cirrhosis (observed from March 2015 to July 2019) was performed to identify patients with CT imaging and outcomes data. For each patient, clinical and biochemical data were collected, and the presence, types, and sizes of SPSSs were investigated with CT. Patients were followed for a mean of 27.5 months ± 22.8. Multivariable logistic analysis was used to identify the clinical characteristics associated with the presence of SPSSs (any size) and presence of SPSSs 1 cm or larger. Competitive risk analysis (Fine and Gray model) was used to identify the association between SPSSs and complications and mortality. Results Two hundred twenty-two patients with cirrhosis (157 male, 65 female; mean age, 62 years ± 12 [standard deviation]) were evaluated. An SPSS was found in 141 of 222 patients (63.5%), and 40 of 222 (18%) had a shunt diameter of at least 1 cm. At presentation, variables independently associated with the presence of SPSSs (any size) were portal vein thrombosis (odds ratio, 5.5; P = .008) and Child-Pugh class C (odds ratio, 3.0; P = .03). Previous hepatic encephalopathy (odds ratio, 4.4; P = .001) and portal vein thrombosis (odds ratio, 5.3; P = .001) were the only variables associated with SPSSs larger than 1 cm. Patients with SPSSs of any size had higher mortality (subdistribution hazard ratio, 1.9; P < .001) and higher frequency of hepatic encephalopathy (subdistribution hazard ratio, 2.3; P = .023), gastrointestinal bleeding (subdistribution hazard ratio, 2.9; P = .039), and portal vein thrombosis (subdistribution hazard ratio, 7.6; P = .005). Conclusion The presence of spontaneous portosystemic shunts on CT images in patients with cirrhosis was associated with higher mortality and complications, including portal vein thrombosis, hepatic encephalopathy, and gastrointestinal bleeding. © RSNA, 2021 See also the editorial by Reeder in this issue.

Effects of sildenafil on right ventricle remodelling in Portopulmonary hypertension.

Portopulmonary hypertension (PoPH) is a clinical condition associated with end-stage liver disease, described by the coexistence of pulmonary arterial hypertension (PAH) and portal hypertension. In PoPH patients, there is a right ventricle (RV) remodeling to compensate for the increased resistance in the lung circulation. There are no studies on the effects of the PAH-targeted pharmacological treatment on the RV dimension and function. The present study summarizes our experience in patients with PoPH treated with sildenafil in a period of 6 years (from 2013 to 2019). We enrolled 64 consecutive patients identified as PoPH, all treated with sildenafil (57.6% in monotherapy; in the other cases in association with macitentan; in 19.0% with initial combination therapy). A hemodynamic invasive cardiopulmonary study was performed at baseline and after 6 months of sildenafil treatment. In our population we showed a significative improvement in RV performance, with a significant increase in RV stroke volume (+33%), RV ejection fraction (+31%) and RV stroke work index (+17.5%). We registered the reduction of the RV cavity dimension over time in all patients treated with sildenafil (RV end diastolic diameter decreased by 15% after 6 months of follow-up). Regarding diastolic function, we highlighted a very significant reduction in RV end-diastolic pressure (-50% concerning baseline). Sildenafil was effective both when used as monotherapy and in combination with macitentan. In conclusion, Sildenafil had a positive impact on RV systolic and diastolic function in patients with PoPH and was able to conditionate the reverse remodeling of the RV.

Prevalence, Predictors, and Severity of Lean Nonalcoholic Fatty Liver Disease in Patients Living With Human Immunodeficiency Virus.

BACKGROUND: The burden of nonalcoholic fatty liver disease (NAFLD) is growing in people living with human immunodeficiency virus (HIV). NAFLD is associated with obesity; however, it can occur in normoweight (lean) patients. We aimed to investigate lean NAFLD in patients living with HIV. METHODS: We included patients living with HIV mono-infection from 3 prospective cohorts. NAFLD was diagnosed by transient elastography (TE) and defined as controlled attenuation parameter ≥248 dB/m, in absence of alcohol abuse. Lean NAFLD was defined when a body mass index was <25 kg/m2. Significant liver fibrosis was defined as TE ≥7.1 kPa. The presence of diabetes, hypertension, or hyperlipidemia defined metabolically abnormal patients. RESULTS: We included 1511 patients, of whom 57.4% were lean. The prevalence of lean NAFLD patients in the whole cohort was 13.9%. NAFLD affected 24.2% of lean patients. The proportions of lean NAFLD patients who were metabolically abnormal or had elevated alanine aminotransferase (ALT) were higher than among those who were lean patients without NAFLD (61.9% vs 48.9% and 36.7% vs 24.2%, respectively). Lean NAFLD patients had a higher prevalence of significant liver fibrosis than lean patients without NAFLD (15.7% vs 7.6%, respectively). After adjusting for sex, ethnicity, hypertension, CD4 cell count, nadir CD4 <200µ/L, and time since HIV diagnosis, predictors of NAFLD in lean patients were age (adjusted OR [aOR], 1.29; 95% confidence interval [CI], 1.04-1.59), high triglycerides (aOR, 1.34; 95% CI, 1.11-1.63), and high ALT (aOR, 1.15; 95% CI, 1.05-1.26), while a high level of high-density lipoprotein cholesterol was protective (aOR, 0.45; 95% CI, .26-.77). CONCLUSIONS: NAFLD affects 1 in 4 lean patients living with HIV mono-infection. Investigations for NAFLD should be proposed in older patients with dyslipidemia and elevated ALT, even if normoweight.

Prediction of Esophageal Varices by Liver Stiffness and Platelets in Persons With Human Immunodeficiency Virus Infection and Compensated Advanced Chronic Liver Disease.

BACKGROUND: People living with human immunodeficiency virus (PLWH) are at increased risk of cirrhosis and esophageal varices. Baveno VI criteria, based on liver stiffness measurement (LSM) and platelet count, have been proposed to avoid unnecessary esophagogastroduodenoscopy (EGD) screening for esophageal varices needing treatment (EVNT). This approach has not been validated in PLWH. METHODS: PLWH from 8 prospective cohorts were included if they fulfilled the following criteria: (1) compensated advanced chronic liver disease (LSM >10 kPa); (2) availability of EGD within 6 months of reliable LSM. Baveno VI (LSM <20 kPa and platelets >150 000/µL), expanded Baveno VI (LSM <25 kPa and platelets >110 000/µL), and Estudio de las Hepatitis Víricas (HEPAVIR) criteria (LSM <21 kPa) were applied to identify patients not requiring EGD screening. Criteria optimization was based on the percentage of EGDs spared, while keeping the risk of missing EVNT <5%. RESULTS: Five hundred seven PLWH were divided into a training (n = 318) and a validation set (n = 189). EVNT were found in 7.5%. In the training set, Baveno VI, expanded Baveno VI, and HEPAVIR criteria spared 10.1%, 25.5%, and 28% of EGDs, while missing 0%, 1.2%, and 2.2% of EVNT, respectively. The best thresholds to rule out EVNT were platelets >110 000/µL and LSM <30 kPa (HIV cirrhosis criteria), with 34.6% of EGDs spared and 0% EVNT missed. In the validation set, HEPAVIR and HIV cirrhosis criteria spared 54% and 48.7% of EGDs, while missing 4.9% and 2.2% EVNT, respectively. CONCLUSIONS: Baveno VI criteria can be extended to HEPAVIR and HIV cirrhosis criteria while sparing a significant number of EGDs, thus improving resource utilization for PLWH with compensated advanced chronic liver disease.