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- Bernal, William, et al.
(författare)
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Aerobic capacity at cardio-pulmonary exercise testing and survival with and without liver transplantation in patients with chronic liver disease
- 2014
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Ingår i: Liver transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1527-6465 .- 1527-6473. ; 20:1, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic liver disease (CLD) is associated with muscle wasting, reduced exercise tolerance and aerobic capacity (AC). Measures of AC determined using cardiopulmonary exercise testing (CPET) may predict post liver transplant (LT) survival, but relation to non-transplant outcome is uncertain. In patients assessed for LT we examined the relation of CPET AC parameters to severity of liver disease, nutritional state and survival with and without LT.Patients and Methods:Patients assessed for elective first LT for who underwent CPET and anthropometric assessment at a single centre were studied. CPET-derived measures of AC evaluated were peak oxygen consumption (VO2 -peak) and Anaerobic Threshold (AT).Results:399 patients underwent CPET and 223 LT; 45% of patients had VO2 -peak <50% predicted and 31% AT<9ml/kg/min. VO2 -peak and AT correlated with MELD but more closely with serum sodium and albumin. Hand grip strength correlated strongly with VO2 -peak. Patients with impaired AC had prolonged post-LT hospitalisation and 1-year post-transplantation non-survivors had lower AT than survivors (p<0.05), significant on multivariate analysis. 176 patients did not undergo LT; 1-year mortality was 34.6%. AT (p<0.05) and VO2 -peak (p<0.001) were lower in non-survivors. On multivariate analysis, AT was independently associated with non-survival.Conclusions:Aerobic capacity is markedly impaired in many patients with CLD. In those not transplanted, impaired AT was predictive of mortality and in those undergoing LT related to post-operative hospitalisation and survival. AC should be evaluated as a modifiable factor to improve patient survival, whether or not LT is anticipated.
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- Patel, Vishal C., et al.
(författare)
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Rifaximin-alpha reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy : RIFSYS randomised controlled trial
- 2022
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 76:2, s. 332-342
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Rifaximin-alpha is efficacious for the prevention of recurrent hepatic encephalopathy (HE), but its mechanism of action remains unclear. We postulated that rifaximin-alpha reduces gut microbiota-derived endotoxemia and systemic inflammation, a known driver of HE. Methods: In a placebo-controlled, double-blind, mechanistic study, 38 patients with cirrhosis and HE were randomised 1:1 to receive either rifaximin-alpha (550 mg BID) or placebo for 90 days. Primary outcome: 50% reduction in neutrophil oxidative burst (OB) at 30 days. Secondary outcomes: changes in psychometric hepatic encephalopathy score (PHES) and neurocognitive functioning, shotgun metagenomic sequencing of saliva and faeces, plasma and faecal metabolic profiling, whole blood bacterial DNA quantification, neutrophil toll-like receptor (TLR)-2/4/9 expression and plasma/faecal cytokine analysis. Results: Patients were well-matched: median MELD (11 rifaximin-alpha vs. 10 placebo). Rifaximin-alpha did not lead to a 50% reduction in spontaneous neutrophil OB at 30 days compared to baseline (p = 0.48). However, HE grade normalised (p = 0.014) and PHES improved (p = 0.009) after 30 days on rifaximin-alpha. Rifaximin-alpha reduced circulating neutrophil TLR-4 expression on day 30 (p = 0.021) and plasma tumour necrosis factor-alpha (TNF-alpha) (p <0.001). Rifaximin-a suppressed oralisation of the gut, reducing levels of mucin-degrading sialidase-rich species, Streptococcus spp, Veillonella atypica and parvula, Akkermansia and Hungatella. Rifaximin-alpha promoted a TNF-alpha-and interleukin17E-enriched intestinal microenvironment, augmenting antibacterial responses to invading pathobionts and promoting gut barrier repair. Those on rifaximin-alpha were less likely to develop infection (odds ratio 0.21; 95% CI 0.05-0.96). Conclusion: Rifaximin-alpha led to resolution of overt and covert HE, reduced the likelihood of infection, reduced oralisation of the gut and attenuated systemic inflammation. Rifaximin-alpha plays a role in gut barrier repair, which could be the mechanism by which it ameliorates bacterial translocation and systemic endotoxemia in cirrhosis.
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