-
1.
Efficacy and safety of direct oral anticoagulants versus vitamin K antagonist for portal vein thrombosis in cirrhosis: A systematic review and meta-analysis.
Koh, JH, Liew, ZH, Ng, GK, Liu, HT, Tam, YC, De Gottardi, A, Wong, YJ
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2022;(1):56-62
Abstract
INTRODUCTION AND AIM Portal vein thrombosis (PVT) is associated with a higher risk of liver-related complications. Recent guidelines recommend direct-acting anticoagulants (DOAC) in patients with cirrhosis and non-tumoral PVT. However, data on the efficacy and safety of DOAC in these patients remain limited. We aim to investigate the efficacy and safety of DOAC compared to vitamin K antagonists (VKA) to treat non-tumoral PVT in patients with cirrhosis. METHODS We performed a systematic search of six electronic databases using MeSH term and free text. We selected all studies comparing the use of DOACs with vitamin K antagonist to treat PVT in cirrhosis. The primary outcome was PVT recanalization. Secondary outcomes were and PVT progression, major bleeding, variceal bleeding and death. RESULTS From 944 citations, we included 552 subjects from a total of 11 studies (10 observational and 1 randomized trial) that fulfilled the inclusion criteria. We found that DOAC were associated with a higher pooled rate of PVT recanalization (RR = 1.67, 95%CI: 1.02, 2.74, I2 = 79%) and lower pooled risk of PVT progression (RR = 0.14, 95%CI: 0.03-0.57, I2 = 0%). The pooled risk of major bleeding (RR = 0.29, 95%CI: 0.08-1.01, I2 = 0%), variceal bleeding (RR = 1.29, 95%CI: 0.64-2.59, I2 = 0%) and death (RR = 0.31, 95%CI: 0.01-9.578, I2 = 80%) was similar between DOAC and VKA. CONCLUSION For the treatment of PVT in patients with cirrhosis, the bleeding risk was comparable between DOAC and VKA. However, DOAC were associated with a higher pooled rate of PVT recanalization. Dedicated randomized studies are needed to confirm these findings.
-
2.
The efficacy of parenteral nutrition (PN) and enteral nutrition (EN) supports in cirrhosis: A systematic review and network meta-analysis.
Yu, B, Wang, J
Medicine. 2022;(3):e28618
-
-
Free full text
-
Abstract
IMPORTANCE Multiple nutritional therapies are currently available for patients with liver cirrhosis, yet many interventions have not been compared head-to-head within randomized clinical trials. OBJECTIVE To evaluate the improvement of nutritional indicators and liver function indexes of liver cirrhosis treated with different nutrition intervention. DATA SOURCE We searched PubMed, Embase. com and Cochrane Library database from construction to April 3, 2020. After eliminating the duplicated or overlapping reports, 6 studies were included. We performed a Bayesian network meta-analysis by Stata 12.0 and GeMTC 0.14.3 in order to compare different nutritional interventions with consistency model. STUDY SELECTION Randomized clinical trials comparing 2 or more therapies in patients with cirrhosis were evaluated. Six randomized clinical trials met the selection criteria. DATA EXTRACTION AND SYNTHESIS Two investigators independently reviewed the full manuscripts of eligible studies and extracted information into an electronic database: patients' characteristics study design, interventions, the number of events of interest in each group. MAIN OUTCOMES AND MEASURES Body mass index, Child-Pugh score, model for end-stage liver disease score, total bilirubin, alanine transaminase, aspartate transaminase, total protein, Triceps skinfold, Midarm Muscle Circumference, Fischer ratio, overall survival. RESULTS There are 6 studies enrolling a total of 1148 patients who received different nutrition supports including parenteral nutrition (PN), enteral nutrition (EN), EN (without branched-chain amino acids), EN + intestinal probiotics, PN + EN, late evening snacks (LES), EN + LES, noLES. The direct comparisons showed that the effect of EN was better than EN (without branched-chain amino acids); EN + intestinal probiotics was better than EN and PN; PN + EN was better than them alone; EN + LES was better than LES and EN; LES was better than noLES. Although the difference of indirect comparisons between the included regimens was not statistically significant, the results showed that EN + intestinal probiotics appeared to be superior to PN + EN. While LES and EN + LES seemed to rank behind them and the difference between them was extremely small. CONCLUSION AND RELEVANCE Available evidence suggests that EN + intestinal probiotics appear to be the most effective strategy for patients with cirrhosis compared with other interventions.
-
3.
Ferroptosis and Liver Fibrosis.
Pan, Q, Luo, Y, Xia, Q, He, K
International journal of medical sciences. 2021;(15):3361-3366
Abstract
Ferroptosis is an iron-dependent form of regulated cell death, which is characterized by a large amount of lipid peroxide accumulation and the imbalance of redox state in cells. Ferroptosis is usually accompanied with the dysfunction of lipid repair enzyme (glutathione peroxidase 4, GPX4), large masses of iron accumulation and lipid peroxidation of polyunsaturated fatty acids (PUFAs). Ferroptosis is related to several signaling pathways, including amino acid and iron metabolism, ferritinophagy, cell adhesion and p53 and Keap1/Nrf2 signaling pathways. A number of studies have indicated that ferroptosis is closely associated with acute renal failure, tumor, ischemia and reperfusion injury, neurodegenerative diseases and liver fibrosis. Liver fibrosis, which has long been a global health problem, still lacks effective treatment till now, and the discovery of ferroptosis provides a new insight into addressing this issue.
-
4.
Expression of NF-κB, IL-6, and IL-10 genes, body composition, and hepatic fibrosis in obese patients with NAFLD-Combined effects of oleoylethanolamide supplementation and calorie restriction: A triple-blind randomized controlled clinical trial.
Tutunchi, H, Ostadrahimi, A, Saghafi-Asl, M, Roshanravan, N, Shakeri-Bavil, A, Asghari-Jafarabadi, M, Farrin, N, Mobasseri, M
Journal of cellular physiology. 2021;(1):417-426
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common noncommunicable diseases worldwide. The present study aimed to investigate the effects of oleoylethanolamide (OEA) supplementation combined with calorie restriction on inflammation, body composition, and hepatic fibrosis among obese patients with NAFLD. In this 12-week randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group. The weight-loss diet was also designed for both groups. Pre- and postintervention messenger RNA expression levels of the transcription factor nuclear factor-κB (NF-κB), interleukin-6 (IL-6) and IL-10, body composition, and NAFLD fibrosis score were assessed. At the end of the study, the OEA group showed lower NF-κB and IL-6 expression levels compared to the placebo (p < .01). However, IL-10 expression level was approximately twofold higher in the OEA group compared to the placebo group (p = .008). A significant reduction was observed in the fat mass of the OEA group compared to the placebo (p = .044) postintervention. In addition, OEA supplementation led to a significant increase in fat-free mass in the OEA group compared to the placebo (p = .032). A remarkable increase was observed in resting metabolic rate (RMR) in the OEA group (p = .009); however, it was not found in the placebo group. There were no significant between-group differences in RMR postintervention. In addition, no significant within-and between-group differences were observed in the NAFLD fibrosis score at the end of the trial. Treatment with OEA along with weight-loss intervention could significantly improve inflammation and body composition in patients with NAFLD.
-
5.
Malnourished cirrhotic patient: what should we do?
Sciarrone, SS, Zanetto, A, Russo, FP, Germani, G, Gambato, M, Battistella, S, Pellone, M, Shalaby, S, Burra, P, Senzolo, M
Minerva gastroenterology. 2021;(1):11-22
Abstract
Malnutrition and sarcopenia have a high prevalence in cirrhotic patients. Frailty generally overlaps with malnutrition and sarcopenia in cirrhosis, leading to increased morbidity and mortality. Rapid nutritional screening assessment should be performed in all patients with cirrhosis, and more specific tests for sarcopenia should be performed in those at high risk. The pathogenesis of malnutrition in cirrhosis is complex and multifactorial and it is not just due to reduction in protein and calorie intake. Nutritional management in malnourished patients with cirrhosis should be undertaken by a multidisciplinary team to achieve adequate protein/calorie intake. While the role of branched-chained amino acids remains somewhat contentious in achieving a global benefit of decreasing mortality- and liver-related events, these latter and vitamin supplements, are recommended for those with advanced liver disease. Novel strategies to reverse sarcopenia such as hormone supplementation, long-term ammonia-lowering agents and myostatin antagonists, are currently under investigation. Malnutrition, sarcopenia and frailty are unique, inter-related and multidimensional problems in cirrhosis which require special attention, prompt assessment and appropriate management as they significantly impact morbidity and mortality.
-
6.
Pharmacotherapy for Weight Loss in Cirrhosis and Liver Transplantation: Translating the Data and Underused Potential.
Brown, SA, Izzy, M, Watt, KD
Hepatology (Baltimore, Md.). 2021;(5):2051-2062
Abstract
BACKGROUND AND AIMS Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to >40% post-transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine-topiramate, naltrexone-bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs). APPROACH AND RESULTS While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine-topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed. CONCLUSIONS The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co-morbidities, and concomitant medications.
-
7.
Primary prevention of variceal bleeding in people with oesophageal varices due to liver cirrhosis: a network meta-analysis.
Roccarina, D, Best, LM, Freeman, SC, Roberts, D, Cooper, NJ, Sutton, AJ, Benmassaoud, A, Plaz Torres, MC, Iogna Prat, L, Csenar, M, et al
The Cochrane database of systematic reviews. 2021;(4):CD013121
-
-
Free full text
-
Abstract
BACKGROUND Approximately 40% to 95% of people with cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed in about one to three years. There are several different treatments to prevent bleeding, including: beta-blockers, endoscopic sclerotherapy, and variceal band ligation. However, there is uncertainty surrounding their individual and relative benefits and harms. OBJECTIVES To compare the benefits and harms of different treatments for prevention of first variceal bleeding from oesophageal varices in adults with liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for prevention of first variceal bleeding from oesophageal varices according to their safety and efficacy. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers to December 2019 to identify randomised clinical trials in people with cirrhosis and oesophageal varices with no history of bleeding. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and oesophageal varices with no history of bleeding. We excluded randomised clinical trials in which participants had previous bleeding from oesophageal varices and those who had previously undergone liver transplantation or previously received prophylactic treatment for oesophageal varices. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the differences in treatments using hazard ratios (HR), odds ratios (OR), and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute for Health and Care Excellence Decision Support Unit guidance. We performed the direct comparisons from randomised clinical trials using the same codes and the same technical details. MAIN RESULTS We included 66 randomised clinical trials (6653 participants) in the review. Sixty trials (6212 participants) provided data for one or more comparisons in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies and those at high risk of bleeding from oesophageal varices. The follow-up in the trials that reported outcomes ranged from 6 months to 60 months. All but one of the trials were at high risk of bias. The interventions compared included beta-blockers, no active intervention, variceal band ligation, sclerotherapy, beta-blockers plus variceal band ligation, beta-blockers plus nitrates, nitrates, beta-blockers plus sclerotherapy, and portocaval shunt. Overall, 21.2% of participants who received non-selective beta-blockers ('beta-blockers') - the reference treatment (chosen because this was the most common treatment compared in the trials) - died during 8-month to 60-month follow-up. Based on low-certainty evidence, beta-blockers, variceal band ligation, sclerotherapy, and beta-blockers plus nitrates all had lower mortality versus no active intervention (beta-blockers: HR 0.49, 95% CrI 0.36 to 0.67; direct comparison HR: 0.59, 95% CrI 0.42 to 0.83; 10 trials, 1200 participants; variceal band ligation: HR 0.51, 95% CrI 0.35 to 0.74; direct comparison HR 0.49, 95% CrI 0.12 to 2.14; 3 trials, 355 participants; sclerotherapy: HR 0.66, 95% CrI 0.51 to 0.85; direct comparison HR 0.61, 95% CrI 0.41 to 0.90; 18 trials, 1666 participants; beta-blockers plus nitrates: HR 0.41, 95% CrI 0.20 to 0.85; no direct comparison). No trials reported health-related quality of life. Based on low-certainty evidence, variceal band ligation had a higher number of serious adverse events (number of events) than beta-blockers (rate ratio 10.49, 95% CrI 2.83 to 60.64; 1 trial, 168 participants). Based on low-certainty evidence, beta-blockers plus nitrates had a higher number of 'any adverse events (number of participants)' than beta-blockers alone (OR 3.41, 95% CrI 1.11 to 11.28; 1 trial, 57 participants). Based on low-certainty evidence, adverse events (number of events) were higher in sclerotherapy than in beta-blockers (rate ratio 2.49, 95% CrI 1.53 to 4.22; direct comparison rate ratio 2.47, 95% CrI 1.27 to 5.06; 2 trials, 90 participants), and in beta-blockers plus variceal band ligation than in beta-blockers (direct comparison rate ratio 1.72, 95% CrI 1.08 to 2.76; 1 trial, 140 participants). Based on low-certainty evidence, any variceal bleed was lower in beta-blockers plus variceal band ligation than in beta-blockers (direct comparison HR 0.21, 95% CrI 0.04 to 0.71; 1 trial, 173 participants). Based on low-certainty evidence, any variceal bleed was higher in nitrates than beta-blockers (direct comparison HR 6.40, 95% CrI 1.58 to 47.42; 1 trial, 52 participants). The evidence indicates considerable uncertainty about the effect of the interventions in the remaining comparisons. AUTHORS' CONCLUSIONS Based on low-certainty evidence, beta-blockers, variceal band ligation, sclerotherapy, and beta-blockers plus nitrates may decrease mortality compared to no intervention in people with high-risk oesophageal varices in people with cirrhosis and no previous history of bleeding. Based on low-certainty evidence, variceal band ligation may result in a higher number of serious adverse events than beta-blockers. The evidence indicates considerable uncertainty about the effect of beta-blockers versus variceal band ligation on variceal bleeding. The evidence also indicates considerable uncertainty about the effect of the interventions in most of the remaining comparisons.
-
8.
[Hyponatremia in children with liver cirrhosis: Treatment strategies].
Imbett-Yepez, S, Peña-Vélez, R, Zárate-Mondragón, F, Ramírez-Mayans, J
Andes pediatrica : revista Chilena de pediatria. 2021;(1):117-121
Abstract
Hyponatremia is a common hydroelectrolytic disorder in pediatric patients with advanced cirrhosis. This complication is related to the alteration in the renal capacity to eliminate free water with solutes such as sodium, which leads to disproportionate water retention, a condition known as dilutional hyponatremia. The main pathogenic factors are the non-osmotic secretion of antidiuretic hormone and the activation of the renin-angiotensin-aldosterone axis and the sympathetic nervous system. Given that hyponatremia in cirrhosis is associated with an increase in morbidity and mortality, the objective of this review is to propose a systematic approach, based on the level of serum sodium, assessment of hemodynamic status and diuresis, which allows precise modifications that minimize negative impacts on survival and neurological sequelae.
-
9.
The role of the gut microbiome in graft fibrosis after pediatric liver transplantation.
Qin, T, Fu, J, Verkade, HJ
Human genetics. 2021;(5):709-724
-
-
Free full text
-
Abstract
Liver transplantation (LT) is a life-saving option for children with end-stage liver disease. However, about 50% of patients develop graft fibrosis in 1 year after LT, with normal liver function. Graft fibrosis may progress to cirrhosis, resulting in graft dysfunction and ultimately the need for re-transplantation. Previous studies have identified various risk factors for the post-LT fibrogenesis, however, to date, neither of the factors seems to fully explain the cause of graft fibrosis. Recently, evidence has accumulated on the important role of the gut microbiome in outcomes after solid organ transplantation. As an altered microbiome is present in pediatric patients with end-stage liver diseases, we hypothesize that the persisting alterations in microbial composition or function contribute to the development of graft fibrosis, for example by bacteria translocation due to increased intestinal permeability, imbalanced bile acids metabolism, and/or decreased production of short-chain fatty acids (SCFAs). Subsequently, an immune response can be activated in the graft, together with the stimulation of fibrogenesis. Here we review current knowledge about the potential mechanisms by which alterations in microbial composition or function may lead to graft fibrosis in pediatric LT and we provide prospective views on the efficacy of gut microbiome manipulation as a therapeutic target to alleviate the graft fibrosis and to improve long-term survival after LT.
-
10.
Adding Branched-Chain Amino Acids to an Enhanced Standard-of-Care Treatment Improves Muscle Mass of Cirrhotic Patients With Sarcopenia: A Placebo-Controlled Trial.
Hernández-Conde, M, Llop, E, Gómez-Pimpollo, L, Fernández Carrillo, C, Rodríguez, L, Van Den Brule, E, Perelló, C, López-Gómez, M, Abad, J, Martínez-Porras, JL, et al
The American journal of gastroenterology. 2021;(11):2241-2249
Abstract
INTRODUCTION The effect of branched-chain amino acid (BCAA) supplementation on muscle mass in patients with cirrhosis and sarcopenia is unknown. METHODS This is a pilot, prospective, randomized, and double-blind study of a cohort of 32 patients with cirrhosis and sarcopenia diagnosed by computed tomography scan who underwent a nutritional and physical activity intervention for 12 weeks. They were divided into 2 groups (placebo: 17 patients; BCAA 15 patients). The study protocol was registered at ClinicalTrials.gov (NCT04073693). RESULTS Baseline characteristics were similar in both groups. After treatment, only the BCAA group presented a significant improvement in muscle mass (43.7 vs 46 cm2/m2; P = 0.023). Seventeen patients (63%) presented improvement in muscle mass overall, which was more frequent in the BCAA group (83.3 vs 46.7%; P = 0.056). Regarding frailty, there was a significant improvement in the Liver Frailty Index in the global cohort (n = 32) after the 12 weeks (4.2 vs 3.9; P < 0.001). This difference was significant in both groups: in the placebo group (4.2 vs 3.8; P < 0.001) and in the BCAA group (4.2 vs 3.9; P < 0.001). After treatment, the BCAA group had a higher increase in zinc levels than the placebo group (Δzinc: 12.3 vs 5.5; P = 0.026). In addition, there was a trend for greater improvement of albumin levels in the BCAA group (Δalbumin: 0.19 vs 0.04; P = 0.091). DISCUSSION BCAA supplementation improves muscle mass in cirrhotic patients with sarcopenia.