Publications by authors named "Manuela Merli"

148 Publications

The improvement in body composition including subcutaneous and visceral fat reduces ammonia and hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.

Liver Int 2021 Sep 20. Epub 2021 Sep 20.

Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy.

Background: Sarcopenia and myosteatosis have been associated to a poor prognosis of cirrhosis and to a higher incidence of hepatic encephalopathy (HE). The prognostic implications of visceral and subcutaneous adiposity are less known.

Aim: to evaluate the modifications of visceral and subcutaneous adipose tissue after TIPS and to investigate their relationships with the modification of muscle mass and with the incidence of post-TIPS HE.

Patients And Methods: 35 cirrhotic patients submitted to TIPS were retrospectively studied. The modification of skeletal muscle index (SMI), muscle attenuation (myosteatosis), subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), assessed by CT-scan and plasma ammonia were evaluated before and after a mean follow-up of 19 ± 15 months after TIPS. The number of episodes of overt HE was also recorded.

Results: During the follow-up, the mean SMI and muscle attenuation increased significantly; SATI significantly increased while VATI significantly decreased, although not uniformly in all patients. By comparing the patients with or without improvement in their nutritional status after TIPS, MELD remained stable while the number of episodes of overt HE was significantly lower in the patients with improved SMI and in the patients with improved SATI. Finally, inverse correlation was observed between the variation of ammonia and SATI (r= -0.40; p< 0.05).

Conclusion: In addition to muscle mass, adipose tissue is modified after TIPS. The improvement of subcutaneous adipose tissue as well as of sarcopenia and myosteatosis is associated to the amelioration of cognitive impairment independently of liver function. The correlation between adipose tissue and ammonia modification may suggest an active role of the adipose tissue in the inter-organ ammonia trafficking.
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http://dx.doi.org/10.1111/liv.15060DOI Listing
September 2021

Safe pregnancy after liver transplantation: Evidence from a multicenter Italian collaborative study.

Dig Liver Dis 2021 Sep 5. Epub 2021 Sep 5.

Multivisceral Transplant Unit, Department of Surgery Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy. Electronic address:

Background: Women who have undergone liver transplantation (LT) enjoy better health, and possibility of childbearing. However, maternal and graft risks, optimal immunosuppression, and fetal outcome is still to clarify.

Aim: Aim of the study was to assess outcomes of pregnancy after LT at national level.

Methods: In 2019, under the auspices of the Permanent Transplant Committee of the Italian Association for the Study of the Liver, a multicenter survey including 14 Italian LT-centers was conducted aiming at evaluating the outcomes of recipients and newborns, and graft injury/function parameters during pregnancy in LT-recipients.

Results: Sixty-two pregnancies occurred in 60 LT-recipients between 1990 and 2018. Median age at the time of pregnancy was 31-years and median time from transplantation to conception was 8-years. During pregnancy, 4 recipients experienced maternal complications with hospital admission. Live-birth-rate was 100%. Prematurity occurred in 25/62 newborns, and 8/62 newborns had low-birth-weight. Cyclosporine was used in 16 and Tacrolimus in 37 pregnancies, with no different maternal or newborn outcomes. Low-birth-weight was correlated to high values of AST, ALT and GGT.

Conclusion: Pregnancy after LT has good outcome; however, maternal complications and prematurity may occur. Compliance with the immunosuppression is fundamental to ensure the stability of graft function and prevent graft-deterioration.
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http://dx.doi.org/10.1016/j.dld.2021.08.013DOI Listing
September 2021

The Effects of 12-Week Beta-Hydroxy-Beta-Methylbutyrate Supplementation in Patients with Liver Cirrhosis: Results from a Randomized Controlled Single-Blind Pilot Study.

Nutrients 2021 Jul 2;13(7). Epub 2021 Jul 2.

Gastroenterology, Department of Translational and Precision Medicine, "Sapienza" University, 00185 Rome, Italy.

Background And Aim: Sarcopenia is considered an important risk factor for morbidity and mortality in liver cirrhosis. Beta-hydroxy-beta-methylbutyrate (HMB) has the potential to increase muscle mass and performance by stimulating protein synthesis and reducing muscle catabolism. The present study aimed at evaluating the effect of HMB supplementation on muscle mass and function in patients with liver cirrhosis. Changes in frailty during the study were also estimated, and the safety of HMB supplementation was verified.

Methods: This is a randomized, single-blind, placebo-controlled pilot trial. Twenty-four patients (14 HMB and 10 placebo) affected by liver cirrhosis were enrolled in the study. Each patient received dedicated counseling, which included nutrition and physical activity recommendations for chronic liver disease patients. Patients were randomized to receive 3 g/day of HMB or placebo (sorbitol powder) for 12 consecutive weeks. A diet interview, anthropometry, electrical bioimpedance analysis (BIA), quadriceps ultrasound, physical performance battery, Liver Frailty Index (LFI), and cognitive tests were completed at enrolment (T0), at 12 weeks (T1), and 24 weeks after enrolment (T2).

Results: At baseline, the two groups were similar in demography, severity of liver disease, muscle mass, muscle function, and cognitive tests. LFI at baseline was higher in patients in the HMB group vs. those in the placebo group (4.1 ± 0.4 vs. 3.4 ± 0.6, < 0.01). After treatment, a statistically significant increase in muscle function was seen in the HMB group (chair stand test: 14.2 ± 5 s vs. 11.7 ± 2.6 s, < 0.05; six-minute walk test: 361.8 ± 68 m vs. 409.4 ± 58 m, < 0.05). Quadriceps muscle mass measured by ultrasound also increased (4.9 ± 1.8 vs. 5.4 ± 1.8 mm, < 0.05) after HMB, while LFI decreased (4.1 ± 0.4 vs. 3.7 ± 0.4, < 0.05). HMB was well tolerated by patients, and no adverse events were documented.

Conclusions: Our study suggests the efficacy of 12-week beta-hydroxy-beta-methylbutyrate supplementation in promoting improvements in muscle performance in compensated cirrhotic patients. LFI was also ameliorated. Further studies with a greater number of patients are required to reinforce this hypothesis.
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http://dx.doi.org/10.3390/nu13072296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308449PMC
July 2021

Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology.

J Hepatol 2021 Jul 29. Epub 2021 Jul 29.

Gastroenterology Unit, ASL Latina, Department of Translational and Precision Medicine, "Sapienza" University of Rome.

Bakground & Aims: Although discrimination of the model for end stage liver disease (MELD) is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discrimination and calibration performance of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intra-hepatic portosystemic shunt (TIPS); classic MELD-Mayo; MELD-UNOS, used by United Network for Organ Sharing (UNOS). Recalibration and model updating were also explored.

Methods: 776 patients submitted to elective TIPS (TIPS cohort), and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses.

Results: Major patient characteristics in TIPS/non-TIPS cohorts were: viral etiology 402/188, alcoholic 185/130, NASH 65/33; mean follow-up± SD 25±9/19±21months; 3-6-12 month mortality were respectively, 57-102-142/31-47-99. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post-hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used for a MELD updating.

Conclusions: In this validation study the MELD performance was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for a MELD updating are proposed.

Lay Summary: While discrimination performance of the Model for End Stage Liver Disease (MELD) is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in two independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis and propose a validated model recalibration. Candidate variables for a MELD updating are proposed.
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http://dx.doi.org/10.1016/j.jhep.2021.07.018DOI Listing
July 2021

Risk of falls in patients with cirrhosis evaluated by timed up and go test: Does muscle or brain matter more?

Dig Liver Dis 2021 Jul 4. Epub 2021 Jul 4.

Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome 00185, Italy.

Background: Minimal hepatic encephalopathy (MHE) is considered a risk factor for falls in patients with liver cirrhosis. However, MHE is prevalent in patients with muscle alterations (sarcopenia and myosteatosis) probably due to the role of muscle in ammonia handling.

Aim: To assess the respective role of muscle alterations and MHE on the risk of falls in cirrhotic patients.

Methods: Fifty cirrhotics were studied for MHE detection by using Psychometric Hepatic Encephalopathy Score (PHES) and Animal Naming Test (ANT). CT scan was used to quantify the skeletal muscle index (SMI) and muscle attenuation, as a measure of myosteatosis. The risk of falls was evaluated by the Timed Up&Go test (TUG). The occurrence of falls during follow up was also detected.

Results: 32 patients (64%) had an abnormal TUG (< 14 s). In the group with TUG ≥ 14 s, MHE (72vs31%, p<0.005) and myosteatosis (94vs50%, p = 0.002) were significantly more frequent than in patients with TUG<14 s. At multivariate the variables independently associated to TUG ≥ 14 s were myosteatosis, MHE and chronic beta-blockers use. During a mean follow-up of 25±16.9 months, 12 patients fell; the percentage of falls was significantly higher in patients with TUG ≥ 14 s (50%vs9%, p = 0.001) as well as in patients with myosteatosis (33%vs6%, p = 0.03), but similar in patients with or without MHE (35%vs15%, NS).

Conclusion: In cirrhotic patients both muscle alterations and cognitive impairment, as well as chronic beta-blockers use, are associated to the risk of falls.
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http://dx.doi.org/10.1016/j.dld.2021.06.019DOI Listing
July 2021

Sarcopenia and frailty in decompensated cirrhosis.

J Hepatol 2021 Jul;75 Suppl 1:S147-S162

Department of Clinical Medicine, Gastroenterology, Sapienza University of Rome, Italy. Electronic address:

In patients with decompensated cirrhosis, sarcopenia and frailty are prevalent. Although several definitions exist for these terms, in the field of hepatology, sarcopenia has commonly been defined as loss of muscle mass, and frailty has been broadly defined as the phenotypic manifestation of the loss of muscle function. Prompt recognition and accurate assessment of these conditions are critical as they are both strongly associated with morbidity, mortality, poor quality of life and worse post-liver transplant outcomes in patients with cirrhosis. In this review, we describe the complex pathophysiology that underlies the clinical phenotypes of sarcopenia and frailty, their association with decompensation, and provide an overview of tools to assess these conditions in patients with cirrhosis. When available, we highlight data focusing on patients with acutely decompensated cirrhosis, such as inpatients, as this is an area of unmet clinical need. Finally, we discuss management strategies to reverse and/or prevent the development of sarcopenia and frailty, which include adequate nutritional intake of calories and protein, as well as regular exercise of at least moderate intensity, with a mix of aerobic and resistance training. Key knowledge gaps in our understanding of sarcopenia and frailty in decompensated cirrhosis remain, including best methods to measure muscle mass and function in the inpatient setting, racial/ethnic variation in the development and presentation of sarcopenia and frailty, and optimal clinical metrics to assess response to therapeutic interventions that translate into a reduction in adverse outcomes associated with these conditions.
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http://dx.doi.org/10.1016/j.jhep.2021.01.025DOI Listing
July 2021

Controlled underdilation using novel VIATORR® controlled expansion stents improves survival after transjugular intrahepatic portosystemic shunt implantation.

JHEP Rep 2021 Jun 3;3(3):100264. Epub 2021 Mar 3.

Department of Internal Medicine I, University of Frankfurt, Frankfurt, Germany.

Background & Aims: Smaller 8-mm diameter transjugular intrahepatic portosystemic shunts (TIPS) appear to be more beneficial than larger 10-mm TIPS stent-grafts, but lack the ability for secondary dilation in cases of clinical ineffectiveness. Underdilated VIATORR® TIPS stent grafts (VTS) expand passively, whereas novel VIATORR Controlled Expansion (VCX) stent grafts do not. This study evaluated the impact on survival of underdilated VCX compared with VTS in patients with decompensated cirrhosis.

Methods: This was a prospective case-control study including patients with cirrhosis receiving TIPS using 10-mm VCX underdilated to 8 mm. Patients with cirrhosis receiving 10-mm VTS underdilated to 8 mm were matched for age, sex, indication for TIPS, and liver function.

Results: A total of 114 patients (47 VCX, 47 VTS, and 20 fully dilated VCX/VTS) were included. After TIPS implantation, underdilated VCX diameter was 8.0 (7.8-9.2) mm at a median time of 359 (87-450) days, compared with VTS at 9.9 (9.7-10.0) mm ( <0.001). The portosystemic pressure gradient immediately after TIPS procedure and after 7 days did not change significantly in VCX [mean 9.4 (± 0.8) 10.4 (± 0.7) mmHg,  = 0.115). Hospital readmission rates for hepatic encephalopathy were 23% (n = 11) 51% (n = 24) for VCX and VTS ( <0.001), respectively. Patients with VCX had significantly lower rates of large-volume paracentesis (n = 5 [11%] n = 10 [21%],  = 0.017) and heart failure (n = 1 [2%] n = 7 [15%],  = 0.015). One-year mortality for underdilated VCX and VTS was 15% (n = 7) and 30% (n = 14) and, for fully dilated VCX/VTS, was 45% (n = 9) (log-rank  = 0.008), respectively.

Conclusions: This study demonstrated that VCX stent grafts underdilated to 8 mm do not passively expand to nominal diameter and suggests reduced hospital readmissions because of hepatic encephalopathy, uncontrolled ascites, and heart failure, and improved 1-year survival compared with underdilated VTS.

Lay Summary: Transjugular intrahepatic portosystemic shunt (TIPS) improves survival in selected patients with liver cirrhosis and acute variceal bleeding or refractory ascites. Smaller 8-mm diameter TIPS stent grafts appear to improve patient outcome compared with larger 10-mm diameter stent grafts. Novel VIATORR® Controlled Expansion (VCX) stent grafts facilitate safe and stable underdilation to 8 mm of large 10-mm diameter stent grafts with improved patient outcome (survival, hepatic encephalopathy, ascites and heart failure) compared with legacy VIATORR TIPS stent graft (VTS). Thus, the use of underdilated VCX could preserve heart function.

Clinical Trials Registration: The study is registered at Clinicaltrials.govNCT03628807.
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http://dx.doi.org/10.1016/j.jhepr.2021.100264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113713PMC
June 2021

Nutrition in Chronic Liver Disease: Consensus Statement of the Indian National Association for Study of the Liver.

J Clin Exp Hepatol 2021 Jan-Feb;11(1):97-143. Epub 2020 Oct 1.

Department of Gastroenterology, SPS Hospital, Ludhiana, 141001, India.

Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders.
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http://dx.doi.org/10.1016/j.jceh.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897902PMC
October 2020

Ustekinumab for the treatment of moderate-to-severe plaque psoriasis in a solid organ transplanted recipient: A case report.

Australas J Dermatol 2021 Aug 26;62(3):e442-e443. Epub 2021 Feb 26.

Department of Precision and Translational Medicine, Centre for the Diagnosis and Treatment of Portal Hypertension, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1111/ajd.13568DOI Listing
August 2021

[The European Association for the Study of Liver (EASL) nutrition guidelines.]

Recenti Prog Med 2021 Feb;112(2):103-109

Dipartimento di Medicina Traslazionale e di Precisione, Sapienza Università di Roma.

This review explores the latest guidelines on nutrition in patients with chronic liver diseases of the European Association for the Study of the Liver (EASL) and recent studies on physiopathology, clinical outcomes and possible treatments of malnutrition and sarcopenia in liver cirrhosis. Chronic liver diseases are frequently associated with malnutrition, changes in skeletal muscle and bone quality and quantity. About 20% of patients with compensated liver cirrhosis and 50% of those with decompensated cirrhosis are sarcopenic. Malnutrition and sarcopenia are associated with a higher complication rate (ascites, bacterial infections and hepatic encephalopathy) and are independent predictors of lower survival in cirrhotic patients. In recent years, concomitant with the decline of post-viral cirrhosis, patients affected by post-metabolic cirrhosis are increasing. These patients are more frequently overweight or obese, but sarcopenia may also coexist. Sarcopenic obesity has been shown to worsen the prognosis in patients with liver cirrhosis. There is a general consensus about the need of improving the nutritional status and implementing skeletal muscle mass in cirrhotic patients, but this is not always achievable. Osteoporosis is present in about 30% of cirrhotic patients, with a higher prevalence in patients with cholestasis. Treatment with phosphonates, calcium and vitamin D are recommended in association with a periodic follow-up.
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http://dx.doi.org/10.1701/3559.35370DOI Listing
February 2021

Cumulative incidence of solid and hematological De novo malignancy after liver transplantation in a multicentre cohort.

Ann Hepatol 2021 Sep-Oct;24:100309. Epub 2021 Jan 20.

Gastroenterology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy. Electronic address:

Background: Recent innovations in the field of liver transplantation have led to a wealth of new treatment regimes, with potential impact on the onset of de novo malignancies (DNM). The aim of this multicenter cohort study was to provide contemporary figures for the cumulative incidences of solid and hematological DNM after liver transplantation.

Methods: We designed a retrospective cohort study including patients undergoing LT between 2000 and 2015 in three Italian transplant centers. Cumulative incidence was calculated by Kaplan-Meyer analysis.

Results: The study included 789 LT patients with a median follow-up of 81 months (IQR: 38-124). The cumulative incidence of non-cutaneous DNM was 6.2% at 5-years, 11.6% at 10-years and 16.3% at 15-years. Post-Transplant Lymphoproliferative Disorders (PTLD) were demonstrated to have a cumulative incidence of 1.0% at 5-years, 1.6% at 10-years and 2.2% at 15-years. Solid Organ Tumors (SOT) demonstrated higher cumulative incidences - 5.3% at 5-years, 10.3% at 10-years and 14.4% at 15-years. The most frequently observed classifications of SOT were lung (rate 1.0% at 5-years, 2.5% at 10-years) and head & neck tumors (rate 1.3% at 5-years, 1.9% at 10-years).

Conclusions: Lung tumors and head & neck tumors are the most frequently observed SOT after LT.
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http://dx.doi.org/10.1016/j.aohep.2021.100309DOI Listing
January 2021

PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis.

J Hepatol 2021 05 20;74(5):1097-1108. Epub 2020 Nov 20.

Medical University of Innsbruck, Innsbruck, Austria.

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes.

Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome.

Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90-day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality.

Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis.

Lay Summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes.
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http://dx.doi.org/10.1016/j.jhep.2020.11.019DOI Listing
May 2021

ESPEN practical guideline: Clinical nutrition in liver disease.

Clin Nutr 2020 12 27;39(12):3533-3562. Epub 2020 Oct 27.

Department of Internal Medicine, Municipal Hospital of Dessau, Dessau, Germany.

Background: The Practical guideline is based on the current scientific ESPEN guideline on Clinical Nutrition in Liver Disease.

Methods: It has been shortened and transformed into flow charts for easier use in clinical practice. The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease.

Results: A total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in liver patients and on liver complications associated with medical nutrition.

Conclusion: This practical guideline gives guidance to health care providers involved in the management of liver disease to offer optimal nutritional care.
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http://dx.doi.org/10.1016/j.clnu.2020.09.001DOI Listing
December 2020

Outcomes of long-term anticoagulant treatment for the secondary prophylaxis of splanchnic venous thrombosis.

Eur J Clin Invest 2021 Jan 11;51(1):e13356. Epub 2020 Aug 11.

Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.

Background: Splanchnic vein thrombosis (SVT) is an uncommon but potentially life-threatening disease usually related to different underlying clinical conditions. The risk of SVT recurrences is high over time in patients with an underlying permanent prothrombotic condition. Vitamin K antagonists (VKA) represent the mainstay of treatment for SVT. Data about the efficacy and safety of direct oral anticoagulants (DOACs) are reported in the literature for the treatment of acute SVT, but less is known about their application for the secondary prophylaxis of venous thromboembolism (VTE). The aim of this study was to assess the efficacy and safety of long-term DOACs therapy in patients at high-risk of thrombosis, compared to VKA.

Methods: This is a retrospective single-centre study including 70 patients with SVT on long-term anticoagulant treatment with VKA followed-up at our Units between January 2017 and December 2019. All the patients were at high thrombotic risk defined as the presence of a permanent prothrombotic condition requiring long-term anticoagulation. During follow-up, 28 patients were shifted to DOACs and their clinical outcomes were compared to those of the patients who continued VKA therapy. All the arterial and venous thrombotic events of the splanchnic and extra-splanchnic districts as well as the haemorrhagic adverse events occurring during follow-up were recorded.

Results: Of the seventy patients enrolled in the study, 36 patients (51.4%) had a single-segment involvement thrombosis (28.5% of portal vein, 7.1% of superior mesenteric vein, 4.3% of splenic vein, 11.5% of hepatic veins) and 34 patients (48.6%) had multi-segment involvement at the time of diagnosis. 42 patients (60%) continued VKA therapy and 28 (40%) were switched to DOACs. Median follow-up was 6 years (range 2-8) during VKA and 1.9 years (range 1-5.2) during DOACs. The incidence of thrombotic events was similar between patients on VKA and those on DOACs. Patients on VKA developed deep vein thrombosis (DVT), and of the patients on DOACs 1 developed NSTEMI and 1 DVT. No major haemorrhagic events occurred. Minor bleedings occurred in 26% of patients on VKA and in none of the DOACs patients (P: 0.09).

Conclusions: Our results highlight that DOACs could represent an effective and safe alternative to the VKA for secondary prophylaxis in SVT patients at high risk of thrombosis.
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http://dx.doi.org/10.1111/eci.13356DOI Listing
January 2021

Nutrition in cirrhosis: Dos and Don'ts.

Authors:
Manuela Merli

J Hepatol 2020 12 3;73(6):1563-1565. Epub 2020 Sep 3.

Department of Translational and Precision Medicine. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2020.07.019DOI Listing
December 2020

Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure.

J Hepatol 2021 02 8;74(2):330-339. Epub 2020 Aug 8.

Department of Internal Medicine IV, Jena University Hospital, Jena, Germany; Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.

Background & Aims: Bacterial infections can trigger the development of organ failure(s) and acute-on-chronic liver failure (ACLF). Geographic variations in bacteriology and clinical practice could lead to worldwide differences in ACLF epidemiology, phenotypes and associated outcomes. Herein, we aimed to evaluate regional differences in bacterial infection-related ACLF in patients with cirrhosis admitted to hospital.

Methods: This post hoc analysis included 1,175 patients with decompensated cirrhosis (with bacterial infection on admission or nosocomial infection) from 6 geographic regions worldwide. Clinical, laboratory and microbiological data were collected from the diagnosis of infection. Patients were followed-up for organ failure(s) and ACLF development according to the EASL-CLIF criteria from enrolment to discharge/death.

Results: A total of 333 patients (28%) had ACLF at diagnosis of infection, while 230 patients developed ACLF after diagnosis of infection, resulting in an overall rate of bacterial infection related-ACLF of 48%, with rates differing amongst different geographic regions (38% in Southern Europe vs. 75% in the Indian subcontinent). Bacterial infection related-ACLF more frequently developed in younger patients (55 ± 13 vs. 58 ± 14 years), males (73% vs. 62%), patients with alcohol-related cirrhosis (59% vs. 45%) and those with a higher baseline MELD score (25 ± 11 vs. 16 ± 5) (all p <0.001). Spontaneous bacterial peritonitis, pneumonia or infections caused by extensively drug resistant (XDR) bacteria were more frequently associated with ACLF development. More patients with ACLF had a positive quick sequential organ failure assessment score and septic shock, resulting in a lower infection resolution rate (all p <0.001).

Conclusions: Bacterial infections, especially with XDR organisms, are associated with the highest risk of ACLF development, accounting for almost half of cases globally. Geographic differences result in variable epidemiology and clinical outcomes.

Lay Summary: Bacterial infections can trigger a sudden deterioration in an otherwise stable cirrhotic patient, a condition known as acute-on-chronic liver failure or ACLF. This study has found that the development of ACLF following bacterial infection occurs most commonly in the Indian subcontinent and less so in Southern Europe. The common infections that can trigger ACLF include infection of the abdominal fluid, known as spontaneous bacterial peritonitis, pneumonia and by bacteria that are resistant to multiple antibiotics. Patients who develop ACLF following a bacterial infection have high death rates and are frequently unable to clear the infection.
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http://dx.doi.org/10.1016/j.jhep.2020.07.046DOI Listing
February 2021

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology.

J Hepatol 2020 10 13;73(4):842-854. Epub 2020 Jul 13.

CHTMAD Vila Real, Vila Real, Portugal.

Background & Aims: Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF.

Methods: A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded.

Results: Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC).

Conclusions: Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. CLINICALTRIALS.

Gov Number: NCT03056612.

Lay Summary: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk.
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http://dx.doi.org/10.1016/j.jhep.2020.06.013DOI Listing
October 2020

Nutrition in Liver Cirrhosis and Transplantation-Current State and Knowledge Gaps.

Nutrients 2020 Mar 3;12(3). Epub 2020 Mar 3.

Gastroenterology, Department of Clinical Medicine, Sapienza University of Rome, 00185 Rome, Italy.

Cirrhosis of the liver is a leading cause of morbidity and mortality [1].[...].
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http://dx.doi.org/10.3390/nu12030680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146315PMC
March 2020

Weight Gain and Metabolic Disorders after Liver Transplantation.

Nutrients 2019 Dec 10;11(12). Epub 2019 Dec 10.

Department of Translational and Precision medicine, Sapienza University of Rome, Italy Viale dell'Università 37, 00185 Roma, Italy.

The development of nutritional and metabolic abnormalities represents an important burden in patients after liver transplantation (LT). Our study aimed at evaluating the incidence, time of onset, and risk factors for nutritional and metabolic abnormalities in patients after LT. The study was a single-center retrospective study. Consecutive patients undergoing elective LT from 2000 to 2016 were enrolled. The presence of at least two among arterial hypertension (AH), diabetes mellitus (DM), dyslipidemia, and obesity (BMI ≥ 30 Kg/m) was utilized to define patients with the metabolic disorder (MD). Three hundred and fifteen patients were enrolled; the median age was 56 years (68% males). Non-alcoholic steatohepatitis (NASH) was the origin of liver disease in 10% of patients. During follow-up, 39% of patients developed AH, 18% DM, and 17% dyslipidemia. Metabolic disorders were observed in 32% of patients. The NASH etiology (OR: 6.2; CI 95% 0.5-3; = 0.003) and a longer follow-up (OR: 1.2; CI 95% 0.004-0.02; = 0.002) were associated with de novo MD. In conclusion, nutritional and metabolic disorders are a frequent complication after LT, being present in up to one-third of patients. The NASH etiology and a longer distance from LT are associated with de novo MD after LT.
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http://dx.doi.org/10.3390/nu11123015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950162PMC
December 2019

The additive value of sarcopenia, myosteatosis and hepatic encephalopathy in the predictivity of model for end-stage liver disease.

Dig Liver Dis 2019 11 7;51(11):1508-1512. Epub 2019 Oct 7.

Dept. of Precision and Translational Medicine, Centre for the Diagnosis and Treatment of Portal Hypertension, "Sapienza" University of Rome, Rome, Italy.

Background: Since the use of the Model for End-Stage Liver Disease (MELD) score for establishing the prognosis of cirrhotic patients has been introduced, questions have been raised whether complications of liver cirrhosis would provide additional information. Myosteatosis, sarcopenia and hepatic encephalopathy (HE) are frequent in cirrhosis and may affect prognosis. Aim of the study was analyzing if these factors are independently related to survival and may improve the accuracy of MELD.

Methods: 249 cirrhotics that underwent abdominal CT-scan were enrolled. For each patient, information about previous episodes of HE and muscle alterations were obtained. Patients were followed until transplantation or death.

Results: History of HE, MELD, sarcopenia and myosteatosis were independently associated with mortality. The MELD-Sarco-Myo-HE score added accuracy to the MELD score alone for 6- and 3-months mortality. By removing HE, as the only not quantifiable parameter of the model, no relevant decrease in accuracy for 6- and 3-months mortality detection was observed.

Conclusions: The accuracy of MELD in predicting 3- and 6-months mortality may be improved by considering the muscle alterations. A model considering the above parameters may classify more accurately over 30% of the patients.
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http://dx.doi.org/10.1016/j.dld.2019.09.004DOI Listing
November 2019

The Effect of 12 Weeks of β-Hydroxy-β-Methyl-Butyrate Supplementation after Liver Transplantation: A Pilot Randomized Controlled Study.

Nutrients 2019 Sep 19;11(9). Epub 2019 Sep 19.

Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.

Sarcopenia is a frequent complication in liver transplant (LT) recipients. β-hydroxy-β-methyl-butyrate (HMB) has the potential to increase muscle-performance and tropism. Our study aims at evaluating the effect on muscle mass and functioning, and the safety of 12 weeks of HMB supplementation in patients after LT. This is a pilot, randomized study. Male patients undergoing LT were randomly assigned to the HMB or control group. A diet interview, anthropometry and body composition by dual energy X-ray absorptiometry (DEXA) were performed at enrollment (T0), after 12 weeks (T1) and after 12 months (T12). Twenty-two liver transplant male patients were enrolled in the study: 12 in the HMB group and 10 as the control group. At enrollment, demographic, clinical and nutritional data were similar. According to the appendicular skeletal muscle index, sarcopenia was present in 50% of patients. The appendix skeletal muscle mass index (ASMI) showed a significant increase at T1 and T12 in HMB patients, but not in controls. The mid-arm muscle-circumference and hand grip strength also increased at T1 and T12 versus T0 only in the HMB group. No side effects were reported in either group. The study showed a positive effect of HMB in the recovery of muscle mass and strength after LT. HMB supplement in patients after LT was safe and well tolerated.
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http://dx.doi.org/10.3390/nu11092259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769827PMC
September 2019

Pediatric sarcopenia: exploring a new concept in children with chronic liver disease.

Authors:
Manuela Merli

J Pediatr (Rio J) 2020 Jul - Aug;96(4):406-408. Epub 2019 Aug 27.

Sapienza University of Rome, Department of Translational and Precision Medicine, Gastroenterology and Hepatology Unit, Rome, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jped.2019.08.001DOI Listing
October 2020

Efficacy of Albumin Treatment for Patients with Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis.

Clin Gastroenterol Hepatol 2020 04 5;18(4):963-973.e14. Epub 2019 Aug 5.

EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain.

Background & Aims: We performed a randomized trial to determine whether albumin should be administered to patients with infections unrelated to spontaneous bacterial peritonitis (SBP).

Methods: We performed a multicenter, open-label trial in which 118 patients with cirrhosis, non-SBP infections, and additional risk factors for poor outcome were randomly assigned to receive antibiotics plus albumin (study group; n = 61) or antibiotics alone (control group; n = 57). The primary outcome was in-hospital mortality; secondary outcomes were effect of albumin on disease course.

Results: There were no significant differences at baseline between groups in results from standard laboratory tests, serum markers of inflammation, circulatory dysfunction, or liver severity scores. However, the combined prevalence of acute on chronic liver failure (ACLF) and kidney dysfunction was significantly higher in the study group (44.3% vs 24.6% in the control group; P = .02), indicating greater baseline overall severity. There was no significant difference in the primary outcome between groups (13.1% in the study group vs 10.5% in the control group; P = .66). Circulatory and renal functions improved in only the study group. A significantly higher proportion of patients in the study group had resolution of ACLF (82.3% vs 33.3% in the control group; P = .03). A significantly lower proportion of patients in the study group developed nosocomial infections (6.6% vs 24.6% in the control group; P = .007).

Conclusions: In a randomized trial of patients with advanced cirrhosis and non-SBP infections, in-hospital mortality was similar between those who received albumin plus antibiotics vs those who received only antibiotics (controls). However, patients given albumin were sicker at baseline and, during the follow-up period, a higher proportion had ACLF resolution and a lower proportion had nosocomial infections. ClinicalTrials.gov no: NCT02034279.
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http://dx.doi.org/10.1016/j.cgh.2019.07.055DOI Listing
April 2020

Donor Small-Droplet Macrovesicular Steatosis Affects Liver Transplant Outcome in HCV-Negative Recipients.

Can J Gastroenterol Hepatol 2019 2;2019:5862985. Epub 2019 May 2.

Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.

Background: No data are available on liver transplantation (LT) outcome and donor liver steatosis, classified as large droplet macrovesicular (Ld-MaS), small-droplet macrovesicular (Sd-MaS), and true microvesicular (MiS), taking into account the recipient Hepatitis C virus (HCV) status.

Aim: We investigate the impact of allograft steatosis reclassified according to the Brunt classification on early graft function and survival after LT.

Methods: We retrospectively reviewed 204 consecutive preischemia biopsies of grafts transplanted in our center during the period 2001-2011 according to recipient HCV status.

Results: The median follow-up after LT was 7.5 years (range: 0.0-16.7). In negative recipients (n=122), graft loss was independently associated with graft Sd-MaS, in multivariable Cox regression models comprehending only pre-/intraoperative variables (HR=1.03, 95%CI=1.01-1.05; =0.003) and when including indexes of early postoperative graft function (HR=1.04, 95%CI=1.02-1.06; =0.001). Graft Sd-MaS>15% showed a risk for graft loss > 2.5-folds in both the models. Graft Sd-MaS>15% was associated with reduced graft ATP content and, only in HCV- recipients, with higher early post-LT serum AST peaks.

Conclusions: In HCV-negative recipients, allografts with >15% Sd-MaS have significantly reduced graft survival and show low ATP and higher AST peaks in the immediate posttransplant period. Donors with >15% Sd-MaS have significantly higher BMI, longer ICU stays, and lower PaO2.
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http://dx.doi.org/10.1155/2019/5862985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521523PMC
May 2020

Prevalence and impact of sarcopenia in non-cirrhotic portal hypertension.

Liver Int 2019 10 26;39(10):1937-1942. Epub 2019 Jun 26.

Department of Translational and Precision Medicine, Centre for the Diagnosis and Treatment of Portal Hypertension, "Sapienza" University of Rome, Rome, Italy.

Background & Aims: Little is known on nutritional parameters in patients with chronic portal vein thrombosis (PVT) and idiopathic non-cirrhotic portal hypertension (INCPH). The study aims to assess the prevalence and the clinical impact of sarcopenia in patients with non-cirrhotic portal hypertension (NCPH). A control group of cirrhotic patients was also studied. Both groups were followed up to establish the relationship between sarcopenia and clinical outcomes.

Methods: Sixty-seven patients with NCPH (51 PVT and 16 INCPH) were included in the study group and 104 patients with liver cirrhosis in the control group. The axial plane passing through the intersomatic disk between L3 and L4 was evaluated for the quantitative analysis of muscle mass and the skeletal muscle index (SMI) was calculated. The presence of sarcopenia was established according to SMI validated cut off.

Results: Sarcopenia was present in the 38% of patients with INCPH, 35% of patients with chronic PVT, 32% of patients with compensated cirrhosis and 54% of decompensated cirrhotics. During a mean follow-up of 51 ± 62 months, there was no difference in sarcopenic and non-sarcopenic patients with NCPH for incidence of ascites, hepatic encephalopathy, esophageal varices, variceal bleeding and death. However, the incidence of refractory variceal bleeding requiring TIPS placement was significantly higher in comparison with the non-sarcopenic ones (29% vs 7%, P = 0.01 at log-rank test).

Conclusions: In patients with NCPH sarcopenia is similar to that observed in cirrhotic patients. Moreover, the rate of refractory variceal bleeding was higher in sarcopenic patients suggesting a clinical negative impact of muscle depletion.
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http://dx.doi.org/10.1111/liv.14160DOI Listing
October 2019

Muscle Alterations Are Associated With Minimal and Overt Hepatic Encephalopathy in Patients With Liver Cirrhosis.

Hepatology 2019 11 28;70(5):1704-1713. Epub 2019 Jun 28.

Department of Clinical Medicine, Centre for the Diagnosis and Treatment of Portal Hypertension, "Sapienza" University of Rome, Rome, Italy.

Muscle alterations (myosteatosis and sarcopenia) are frequent in cirrhosis and related to some complications including overt hepatic encephalopathy (HE). The aim of our study was to investigate the relationship between muscle alterations and minimal HE (MHE) and their role in the risk of overt HE. Sixty-four patients with cirrhosis were administered the Psychometric Hepatic Encephalopathy Score and animal naming test to detect MHE. Computed tomography was used to analyze the skeletal muscle index and attenuation. The incidence of the first episode of HE, taking into account the competing risk nature of the data, was estimated. Myosteatosis was observed in 24 patients (37.5%), sarcopenia in 37 (58%), and MHE in 32 (50%). Both myosteatosis (62.5% versus 12.5%, P < 0.001) and sarcopenia (84% versus 31%, P < 0.001) were more frequent in patients with MHE. The variables independently associated with the presence of MHE were sarcopenia, previous overt HE, and myosteatosis. Thirty-one (48%) patients developed overt HE over 16.1 ± 13 months; myosteatosis was detected in 68% and sarcopenia in 84% of them. Sarcopenia and myosteatosis were also independently associated with the development of overt HE. Venous ammonia was significantly higher in patients with sarcopenia (62.6 ± 17.7 versus 41.4 ± 16.1 μg/dL, P < 0.001) and in patients with myosteatosis (65.2 ± 19.2 versus 46.7 ± 17.1 μg/dL, P < 0.001) and inversely correlated to both parameters. Survival was significantly lower in malnourished patients compared to patients without myosteatosis or sarcopenia (P < 0.001). Conclusion: Myosteatosis and sarcopenia, probably by reducing the handling of ammonia in the muscle, are independently associated with MHE and the risk of overt HE in patients with cirrhosis; in malnourished patients, the amelioration of nutritional status may be a goal to decrease both the prevalence of MHE and the incidence of overt HE.
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http://dx.doi.org/10.1002/hep.30692DOI Listing
November 2019

Reply.

Hepatology 2019 08;70(2):762-763

Department of Clinical Medicine, "Sapienza" University of Rome, Rome, Italy.

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http://dx.doi.org/10.1002/hep.30639DOI Listing
August 2019

Sarcopenia Is Associated With Development of Acute-on-Chronic Liver Failure in Decompensated Liver Cirrhosis Receiving Transjugular Intrahepatic Portosystemic Shunt.

Clin Transl Gastroenterol 2019 04;10(4):e00025

Department of Internal Medicine I, University of Bonn, Bonn, Germany.

Introduction: Muscle mass has been shown to be a prognostic marker in patients with liver cirrhosis. Transversal psoas muscle thickness normalized by height (TPMT/height) obtained by routine computed tomography is a simple surrogate parameter for sarcopenia. TPMT/height, however, is not sex specific, which might play a role in risk stratification. Its association with acute-on-chronic liver failure (ACLF) has not been established yet. ACLF is associated with systemic inflammatory dysregulation. This study aimed at evaluating the role of sarcopenia in ACLF development of patients with decompensated cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS) using sex-specific TPMT/height.

Methods: One hundred eighty-six patients from the prospective Non-invasive Evaluation Program for TIPS and Follow Up Network cohort (observational, real-world TIPS cohort with structured follow-up) were analyzed. TPMT/height was measured from routine computed tomography. The sex-specific cutoff was determined to classify patients as sarcopenic and nonsarcopenic for 1-year mortality after TIPS. Clinical outcome was compared. Primary end points were ACLF and 1-year mortality after TIPS. Secondary end points were development of decompensations (hepatic encephalopathy and ascites) after TIPS.

Results: The sex-specific cutoff increases the diagnostic accuracy with regard to primary and secondary end points compared with the unisex cutoff. Sex-specific sarcopenia classification is an independent predictor of 1-year mortality and ACLF development in patients with cirrhosis receiving TIPS. Patients in the sarcopenia group showed significantly higher rates of mortality, ascites, overt hepatic encephalopathy, and ACLF after TIPS compared with the nonsarcopenia group. The Chronic Liver Failure Consortium Acute Decompensation score as a marker of systemic inflammation was significantly higher in sarcopenic patients.

Conclusions: This study demonstrates for the first time that sarcopenia is related to ACLF development and systemic inflammation. The prognostic value of TPMT/height can be improved by using sex-specific cutoffs. ClinicalTrials.gov identifier: NCT03584204.
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http://dx.doi.org/10.14309/ctg.0000000000000025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602782PMC
April 2019

Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis.

Gastroenterology 2019 07 22;157(1):149-162. Epub 2019 Mar 22.

Department of Gastroenterology, Hospital Ramón y Cajal and CIBERehd, Madrid, Spain.

Background & Aims: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections.

Methods: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study).

Results: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines.

Conclusions: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.
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http://dx.doi.org/10.1053/j.gastro.2019.03.021DOI Listing
July 2019
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