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Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide. Curative treatments are available to a minority of patients, as HCC is often diagnosed at an advanced stage. For patients with unresectable and multifocal HCC, tyrosine kinase inhibitor drugs (TKIs) are the only potential treatment option. Despite extensive research, predictors of response to these therapies remain elusive. This study aimed to analyze the biological and histopathological characteristics of HCC patients treated with TKIs, focusing on angiogenesis and lymphangiogenesis. Immunohistochemistry quantified the expression of angiopoietin-2 (Ang2), lymphatic endothelial cells (LEC) podoplanin, and C-type Lectin Domain Family 2 (CLEC-2), key factors in neoangiogenesis and lymphangiogenesis. An increased expression of endothelial Ang2 and LEC podoplanin predicted a lower risk of metastasis. Female patients had significantly longer overall survival and survival on TKIs, associated with higher tumor expression of endothelial Ang2 and LEC podoplanin. Moreover, LEC podoplanin expression and a longer time on TKIs were independently correlated with improved survival on TKI therapy at Cox regression analysis. These findings suggest that endothelial Ang2 and LEC podoplanin could be potential biomarkers for predicting treatment outcomes and guiding therapeutic strategies in HCC patients treated with TKIs.
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BACKGROUND AND 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 AND RESULTS: We retrospectively included patients with PSVD, ≥1 sign of portal hypertension, without a history of variceal bleeding, who underwent an SSM-VCTE within 2 years before or after an upper endoscopy in 21 VALDIG centers, divided into a derivation and a validation cohort. One hundred fifty-four 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. 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% negative predictive value. CONCLUSIONS: This study gathering a total of 309 patients with PSVD 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.
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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 MASLD-related compensated ACLD (MASLD-cACLD). METHODS: This European multicentre study included patients with MASLD-cACLD characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest. RESULTS: A total of 340 patients with MASLD-cACLD (56.2% male; median age 62 [55-68] years, median MELD 8 [7-9], 71.2% with 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 those with 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 (adjusted SHR per mmHg: 1.12, p <0.001). Liver-related mortality occurred in 37 patients at 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 (adjusted SHR per mmHg: 1.20, p <0.001). CONCLUSION: HVPG measurement is of high prognostic value in MASLD-cACLD. In patients with MASLD-cACLD without CSPH, the short-term risk of decompensation is very low and liver-related mortality is rare, while the presence of CSPH substantially increases the risk of both. 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 patients, 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 patients with MASLD-cACLD 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.
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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.
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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.
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Várices Esofágicas y Gástricas , Encefalopatía Hepática , Derivación Portosistémica Intrahepática Transyugular , Humanos , Encefalopatía Hepática/epidemiología , Encefalopatía Hepática/etiología , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Calidad de Vida , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Hemorragia/etiología , Resultado del Tratamiento , Hemorragia Gastrointestinal/etiología , Várices Esofágicas y Gástricas/etiologíaRESUMEN
Portal hypertension (PH) constitutes a pivotal factor in the progression of cirrhosis, giving rise to severe complications and a diminished survival rate. The transjugular intrahepatic portosystemic shunt (TIPS) procedure has undergone significant evolution, with advancements in stent technology assuming a central role in managing PH-related complications. This review aims to outline the progression of TIPS and emphasizes the significant influence of stent advancement on its effectiveness. Initially, the use of bare metal stents (BMSs) was limited due to frequent dysfunction. However, the advent of expanding polytetrafluoroethylene-covered stent grafts (ePTFE-SGs) heralded a transformative era, greatly enhancing patency rates. Further innovation culminated in the creation of ePTFE-SGs with controlled expansion, enabling precise adjustment of TIPS diameters. Comparative analyses demonstrated the superiority of ePTFE-SGs over BMSs, resulting in improved patency, fewer complications, and higher survival rates. Additional technical findings highlight the importance of central stent placement and adequate stent length, as well as the use of smaller calibers to reduce the risk of shunt-related complications. However, improving TIPS through technical means alone is inadequate for optimizing patient outcomes. An extensive understanding of hemodynamic, cardiac, and systemic factors is required to predict outcomes and tailor a personalized approach. Looking forward, the ongoing progress in SG technology, paired with the control of clinical factors that can impact outcomes, holds the promise of reshaping the management of PH-related complications in cirrhosis.
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BACKGROUND AND AIMS: Surveillance programs are strongly recommended in patients with liver cirrhosis for early detection of HCC development. Six-monthly ultrasound sonography is the most reliable and commonly used technique, especially when associated with serum determination of α-fetoprotein, but different score systems have been proposed to overcome the unsatisfactory diagnostic accuracy of α-fetoprotein. The aim of this 12-year prospective study is to compare the gender, age, AFP-L3, AFP, des-gamma-carboxy prothrombin (GALAD) versus age, gender, bilirubin, albumin, and platelets and albumin-bilirubin scores in predicting HCC onset. APPROACH AND RESULTS: A cohort of 545 consecutive patients with compensated advanced chronic liver disease without suspected focal lesions was followed up every 6 months by liver imaging and α-fetoprotein to detect HCC occurrence. Harrell's C-index for censored data was employed to evaluate the performance of any parameters or scores helping to predict HCC development. ROC curve analysis showed that the GALAD score was more accurate in evaluating HCC development than albumin-bilirubin and age, gender, bilirubin, albumin, and platelets. The AUC ranged from 0.7268 to 0.6851 at 5 and 10 years, both in the total cohort and in the sub-cohorts (viral hepatitis, NASH, and alcohol). The HCC Risk model was constructed using univariate and multivariate Cox proportional hazard regression analysis, showing a strong association of GALAD with HR > 1, p < 0.05, in the total and sub-cohorts, and a better risk prediction in the alcohol cohort, both alone and standardized with other blood parameters. CONCLUSIONS: GALAD is the most reliable and accurate score system to detect HCC risk of development in patients with compensated advanced chronic liver disease.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas , Estudios Prospectivos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Albúminas , Bilirrubina , EtanolRESUMEN
Background & Aims: We aimed to evaluate the impact of oesophageal varices (OV) and their evolution on the risk of complications of compensated advanced chronic liver disease (cACLD) caused by non-alcoholic fatty liver disease (NAFLD). We also assessed the accuracy of non-invasive scores for predicting the development of complications and for identifying patients at low risk of high-risk OV. Methods: We performed a retrospective assessment of 629 patients with NAFLD-related cACLD who had baseline and follow-up oesophagogastroduodenoscopy and clinical follow-up to record decompensation, portal vein thrombosis (PVT), and hepatocellular carcinoma. Results: Small and large OV were observed at baseline in 30 and 15.9% of patients, respectively. The 4-year incidence of OV from absence at baseline, and that of progression from small to large OV were 16.3 and 22.4%, respectively. Diabetes and a ≥5% increase in BMI were associated with OV progression. Multivariate Cox regression revealed that small (hazard ratio [HR] 2.24, 95% CI 1.47-3.41) and large (HR 3.86, 95% CI 2.34-6.39) OV were independently associated with decompensation. When considering OV status and trajectories, small (HR 2.65, 95% CI 1.39-5.05) and large (HR 4.90, 95% CI 2.49-9.63) OV at baseline and/or follow-up were independently associated with decompensation compared with the absence of OV at baseline and/or follow-up. The presence of either small (HR 2.8, 95% CI 1.16-6.74) or large (HR 5.29, 95% CI 1.96-14.2) OV was also independently associated with incident PVT. Conclusion: In NAFLD-related cACLD, the presence, severity, and evolution of OV stratify the risk of developing decompensation and PVT. Impact and implications: Portal hypertension is the main driver of liver decompensation in chronic liver diseases, and its non-invasive markers can help risk prediction. The presence, severity, and progression of oesophageal varices stratify the risk of complications of non-alcoholic fatty liver disease. Easily obtainable laboratory values and liver stiffness measurement can identify patients at low risk for whom endoscopy may be withheld, and can also stratify the risk of liver-related complications.
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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.
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Várices Esofágicas y Gástricas , Hipertensión Portal , Humanos , Propranolol/uso terapéutico , Propranolol/farmacología , Várices Esofágicas y Gástricas/complicaciones , Óxido Nítrico Sintasa de Tipo III/farmacología , Óxido Nítrico Sintasa de Tipo III/uso terapéutico , Presión Portal , Óxido Nítrico , Hemorragia Gastrointestinal/prevención & control , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas Adrenérgicos beta/farmacología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Hipertensión Portal/etiología , Hipertensión Portal/complicacionesRESUMEN
Introduction: Hepatic encephalopathy (HE) affects the survival and quality of life of patients with cirrhosis. However, longitudinal data on the clinical course after hospitalization for HE are lacking. The aim was to estimate mortality and risk for hospital readmission of cirrhotic patients hospitalized for HE. Methods: We prospectively enrolled 112 consecutive cirrhotic patients hospitalized for HE (HE group) at 25 Italian referral centers. A cohort of 256 patients hospitalized for decompensated cirrhosis without HE served as controls (no HE group). After hospitalization for HE, patients were followed-up for 12 months until death or liver transplant (LT). Results: During follow-up, 34 patients (30.4%) died and 15 patients (13.4%) underwent LT in the HE group, while 60 patients (23.4%) died and 50 patients (19.5%) underwent LT in the no HE group. In the whole cohort, age (HR 1.03, 95% CI 1.01-1.06), HE (HR 1.67, 95% CI 1.08-2.56), ascites (HR 2.56, 95% CI 1.55-4.23), and sodium levels (HR 0.94, 95% CI 0.90-0.99) were significant risk factors for mortality. In the HE group, ascites (HR 5.07, 95% CI 1.39-18.49) and BMI (HR 0.86, 95% CI 0.75-0.98) were risk factors for mortality, and HE recurrence was the first cause of hospital readmission. Conclusion: In patients hospitalized for decompensated cirrhosis, HE is an independent risk factor for mortality and the most common cause of hospital readmission compared with other decompensation events. Patients hospitalized for HE should be evaluated as candidates for LT.
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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.
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Diagnóstico por Imagen de Elasticidad , Infecciones por VIH , Hipertensión Portal , Humanos , Cirrosis Hepática , Pronóstico , Bazo/diagnóstico por imagen , Plaquetas , Hígado/diagnóstico por imagen , Hígado/patología , Hipertensión Portal/complicaciones , Infecciones por VIH/complicacionesAsunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Nivolumab/efectos adversos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Bevacizumab/efectos adversos , Trasplante de Hígado/efectos adversos , Estudios de Factibilidad , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugíaRESUMEN
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.
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Várices Esofágicas y Gástricas , Derivación Portosistémica Intrahepática Transyugular , Humanos , Anciano , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Várices Esofágicas y Gástricas/etiología , Ascitis/etiología , Ascitis/cirugía , Creatinina , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Sodio , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
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.
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Encefalopatía Hepática , Derivación Portosistémica Intrahepática Transyugular , Humanos , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Ascitis/etiología , Ascitis/cirugía , Resultado del Tratamiento , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Encefalopatía Hepática/etiologíaRESUMEN
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.