Sarcopenia from mechanism to diagnosis and treatment in liver disease

Sarcopenia or loss of skeletal muscle mass is the major component of malnutrition and is a frequent complication in cirrhosis that adversely affects clinical outcomes. These include survival, quality of life, development of other complications and post liver transplantation survival. Radiological image analysis is currently utilized to diagnose sarcopenia in cirrhosis. Nutrient supplementation and physical activity are used to counter sarcopenia but have not been consistently effective because the underlying molecular and metabolic abnormalities persist or are not influenced by these treatments. Even though alterations in food intake, hypermetabolism, alterations in amino acid profiles, endotoxemia, accelerated starvation and decreased mobility may all contribute to sarcopenia in cirrhosis, hyperammonemia has recently gained attention as a possible mediator of the liver-muscle axis. Increased muscle ammonia causes: cataplerosis of α-ketoglutarate, increased transport of leucine in exchange for glutamine, impaired signaling by leucine, increased expression of myostatin (a transforming growth factor beta superfamily member) and an increased phosphorylation of eukaryotic initiation factor 2α. In addition, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy mediated proteolysis, also play a role. These molecular and metabolic alterations may contribute to the anabolic resistance and inadequate response to nutrient supplementation in cirrhosis. Central and skeletal muscle fatigue contributes to impaired exercise capacity and responses. Use of proteins with low ammoniagenic potential, leucine enriched amino acid supplementation, long-term ammonia lowering strategies and a combination of resistance and endurance exercise to increase muscle mass and function may target the molecular abnormalities in the muscle. Strategies targeting endotoxemia and the gut microbiome need further evaluatio

Beta-blokers in patients with cirrhosis and infection: don't blame too soon.

We found that PPI-users had a higher rate and BBs-users a lower rate of infections. The lower infection rate and better prognosis of BB-users can not be attributed, as suggested by Schiavon et al., to a higher proportion of variceal bleeding in this group; in fact, the large majority of patients hospitalized for bleeding were excluded from the study as they came to our ward already on systemic antibiotic treatment (which is usually started in the Emergency room) and this would have represented a confounding factor. Only few patients with variceal bleeding were included: they developed bleeding after enrolment and were equally distributed between those taking and not taking BBs. Following the recent debate about the ‘therapeutic window’ of BBs in cirrhotic patients (2–4), we were also interested in evaluating possible harmful effects of BBs in cirrhotic patients with infections. This was a secondary aim of our study and we certainly recognize that the study was underpowered for this purpose

Albumin infusion in cirrhotic patients with infections other than spontaneous bacterial peritonitis: End of the story?

Non-invasive assessment of liver fibrosis with impulse elastography: Comparison of Supersonic Shear Imaging with ARFI and FibroScan

Interaction between infection and hepatic encephalopathy

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The use of non-selective beta-blockers in patients with cirrhosis: more doubts than certainties

In conclusion, prospective RCT would be needed on the use of NSBBs in decompensated cirrhotic patients with ascites however these trials are difficult to organize and will need a large sample size. A case control study could be useful if the two groups were patients matched for MELD, MELD Na, creatinine, mean arterial pressure, with the same type of ascites (refractory, recurrent, severe) taking or not taking NSBBs. The better and more relevant end pointshould probably be survival. In the meanwhile, the Baveno recommendations can be utilized in clinical practice to remind that severe hypotension is a well-known contraindication for NSBBs which may suggest dose reduction or even therapy discontinuation. Last but not least, NSBBs may have several beneficial effects in patients with cirrhosis beyond the reduction in portal hypertension. They reduce markers of intestinal permeability, bacterial translocation and systemic inflammation, and also the risk of SBP (15,16). The risk to enlarge the indication to stop NSBBs in cirrhotic patients without a real evidence could be as to “throw the baby out with the bath water

Bacterial resistance in cirrhotic patients: An emerging reality

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Presence of multiple bacterial markers in clinical samples might be useful for presumptive diagnosis of infection in cirrhotic patients with culture-negative reports

Bacterial infections in cirrhotic patients with ascites are associated with a severe prognosis and an increased risk of death. The microbiological standard tests for the diagnosis of suspected infection, based on culture test of blood and ascitic fluid, are, in many cases (30-40 %), negative, even when patients show symptoms of infection. A multiple culture-independent protocol was applied and evaluated as a diagnostic and prognostic tool for the detection of bacterial infection in cirrhotic patients. Sixty-four culture-negative samples obtained from 34 cirrhotic patients, with PMN < 250 cells/μl of ascitic fluid, were screened for the presence of bacterial DNA, endotoxin, peptidoglycan/β-glucan and microscopically visible bacterial cells. Correlations between the presence of multiple markers and various clinical and laboratory parameters were evaluated. Bacterial DNA was detected in 23 samples collected from 16 patients; a large part of these samples also showed the presence of other bacterial markers, which was associated with a worsening of liver functionality, a higher incidence of infections during the follow-up and a higher mortality rate in our cohort of cirrhotic patients. We believe that the detection of additional bacterial markers in bacterial DNA-positive clinical samples makes the bacterial presence and its clinical significance more realistic and might be useful as early markers of an ongoing bacterial infection and in establishing a clinical prognosis

Hemostasis in uncontrolled esophageal variceal bleeding by self-expanding metal stents. A systematic review

Aim: The aim of this systematic review was to evaluate the current reported efficacy and the mortality rate of SEMS treatment in uncontrolled bleeding patients. Background: Esophageal variceal bleeding (EVB) represents a life threatening pathology. Despite the adequate pharmacologic and endoscopic treatment, continuous or recurrent bleeding, named as uncontrolled bleeding, occurs in 10-20% of cases. A new removable, covered, and self-expanding metal stent (SEMS) was proposed to control the variceal bleeding. Materials and methods: The study was conducted according to the PRISMA statement. Studies were identified by searching MEDLINE (1989-present) and SCOPUS (1989-present) databases. The last search was run on 01 July 2015. Results: Nine studies (period range=2002-2015) met the inclusion criteria and were included in quantitative analysis. High rate of SEMS efficacy in controling acute bleeding was observed, with a reported percentage ranging from 77.7 to 100%. In 10% to 20% of patients, re-bleeding occurred with SEMS in situ. Stent deployment was successful in 77.8% to 100% of patients while 11 to 36.5% of patients experienced stent migration. Conclusion: SEMS could be effective and safe in control EVB and can be proposed as a reliable option to ballon tamponed for patient stabilization and as a bridging to other therapeutic approach. Keywords: Nonselective β-blockers, TIPSS, Endoscopic band ligation, Uncontrolled bleeding, Selfexpanding metal stent

Sarcopenic obesity in fatty liver

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steato hepatitis have an increasing prevalence among liver diseases. Overweight and obesity are frequently associated conditions in patients with fatty liver. Skeletal muscle mass depletion may also coexist with chronic liver disease even in obese patients. This review will focus on the relationship between sarcopenic obesity and fatty liver

A cost analysis of a broad-spectrum antibiotic therapy in the empirical treatment of health care-associated infections in cirrhotic patients

Background: Early diagnosis and appropriate treatment of infections in cirrhosis are crucial. As new guidelines in this context, particularly for health care-associated (HCA) infections, would be needed, we performed a trial documenting whether an empirical broad-spectrum antibiotic therapy is more effective than the standard one for these infections. Because of the higher daily cost of broad-spectrum than standard antibiotics, we performed a cost analysis to compare: 1) total drug costs, 2) profitability of hospital admissions. Methods: This retrospective observational analysis was performed on patients enrolled in the trial NCT01820026, in which consecutive cirrhotic patients with HCA infections were randomly assigned to a standard vs a broad-spectrum treatment. Antibiotic daily doses, days of treatment, length of hospital stay, and DRG (diagnosis-related group) were recorded from the clinical trial medical records. The profitability of hospitalizations was calculated considering DRG tariffs divided by length of hospital stay. Results: We considered 84 patients (42 for each group). The standard therapy allowed to obtain a first-line treatment cost lower than in the broad-spectrum therapy. Anyway, the latter, being related to a lower failure rate (19% vs 57.1%), resulted in cost saving in terms of cumulative antibiotic costs (first- and second-line treatments). The mean cost saving per patient for the broad-spectrum arm was €44.18 (–37.6%), with a total cost saving of about €2,000. Compared to standard group, we observed a statistically significant reduction in hospital stay from 17.8 to 11.8 days (p<0.002) for patients treated with broad-spectrum antibiotics. The distribution of DRG tariffs was similar in the two groups. According to DRG, the shorter length of hospital stay of the broad-spectrum group involved a higher mean profitable daily cost than standard group (€345.61 vs €252.23; +37%). Conclusion: Our study supports the idea that the use of a broad-spectrum empirical treatment for HCA infections in cirrhosis would be cost-saving and that hospitals need to be aware of the clinical and economic consequences of a wrong antibiotic treatment in this setting. Keywords: profitability, diagnosis-related group, cost saving, antibiotic failur