Dynamics of liver stiffness predicts complications in patients with HCV related cirrhosis treated with direct-acting antivirals.

BACKGROUND: Direct acting antivirals(DAAs) are effective in reducing inflammatory ant fibrotic markers in patients with chronic hepatitis C virus(HCV) infection and to prevent liver-related complications. Two-dimensional shear wave elastography(2D-SWE) is an effective technique for the assessment of liver fibrosis. AIM: To evaluate changes in liver stiffness(LS) in HCV cirrhotic patients undergoing DAA therapy and to identify non-invasive parameters that predict the occurrence of liver-related events. METHODS: We enrolled 229 patients who received DAAs between January 2015 and October 2018. Ultrasound parameters and laboratory data were assessed before treatment and 24(T1) and 48(T2) weeks after end of treatment. Patients were followed up every 6 months to evaluate the development of HCC and other liver related complications. Multiple Cox regression analysis was used to determine parameters associated with the development of complications. RESULTS: Model for End-stage Liver Disease(MELD) score(HR 1.16; CI 95% 1.01-1.33; p = 0.026) and a change in LS at T2(1-year Delta LS) < 20%(HR 2.98; CI 95% 1.01-8.1; p = 0.03) were independently associated with HCC risk. One-year Delta-LS <20% was independently associated with the development of ascites(HR 5.08; CI 95% 1.03 - 25.14; p = 0.04). CONCLUSIONS: Dynamic changes of 2D-SWE-measured LS after DAA therapy may be a useful tool to identify patients who are at higher risk of liver related complications.

Characterization of the gut-liver-muscle axis in cirrhotic patients with sarcopenia.

BACKGROUND & AIM: Sarcopenia is frequent in cirrhosis and is associated with unfavourable outcomes. The role of the gut-liver-muscle axis in this setting has been poorly investigated. The aim of this study was to identify gut microbiota, metabolic and inflammatory signatures associated with sarcopenia in cirrhotic patients. METHODS: Fifty cirrhotic patients assessed for the presence of sarcopenia by the quantification of muscle mass and strength were compared with age- and sex-matched controls. A multiomic analysis, including gut microbiota composition and metabolomics, serum myokines and systemic and intestinal inflammatory mediators, was performed. RESULTS: The gut microbiota of sarcopenic cirrhotic patients was poor in bacteria associated with physical function (Methanobrevibacter, Prevotella and Akkermansia), and was enriched in Eggerthella, a gut microbial marker of frailty. The abundance of potentially pathogenic bacteria, such as Klebsiella, was also increased, to the detriment of autochthonous ones. Sarcopenia was associated with elevated serum levels of pro-inflammatory mediators and of fibroblast growth factor 21 (FGF21) in cirrhotic patients. Gut microbiota metabolic pathways involved in amino acid, protein and branched-chain amino acid metabolism were up-regulated, in addition to ethanol, trimethylamine and dimethylamine production. Correlation networks and clusters of variables associated with sarcopenia were identified, including one centred on Klebsiella/ethanol/FGF21/Eggerthella/Prevotella. CONCLUSIONS: Alterations in the gut-liver-muscle axis are associated with sarcopenia in patients with cirrhosis. Detrimental but also compensatory functions are involved in this complex network.

Minimal Hepatic Encephalopathy is Associated with Increased Cerebral Vascular Resistance. A Transcranial Doppler Ultrasound Study.

Minimal hepatic encephalopathy (MHE) is a subclinical complication of liver cirrhosis with a relevant social impact. Thus, there is urgent need to implement easy to use diagnostic tools for the early identification of affected patients. The aim of this study was to investigate cerebral blood flow, systemic hemodynamics as well as endothelial function of cirrhotic patients with MHE, and to verify their change after treatment with rifaximin. Fifty cirrhotic patients with or without MHE and an equal number of healthy controls underwent transcranial Doppler ultrasound (TCD), abdominal Doppler ultrasound (US), and measurement of flow mediated dilation (FMD). In cirrhotic patients diagnosed with MHE receiving rifaximin, the tests were repeated at the end of treatment. Middle (MCA) and posterior (PCA) cerebral artery resistive (RI) and pulsatility (PI) indices were higher in cirrhotic patients than controls, as well as renal and splenic artery RI. Conversely, FMD was reduced. MCA-RI and PI were even higher in cirrhotic patients with MHE compared to those without; a MCA-RI cut-off of 0.65 showed an accuracy of 74% in discriminating the presence of MHE, with 65% sensitivity and 76% specificity. Rifaximin treatment showed no efficacy in the modulation of cerebral vascular flow. In conclusion, cirrhotic patients with MHE have significantly increased cerebral vascular resistances that are not improved by rifaximin treatment. MCA-RI measurement has a good accuracy for the diagnosis of MHE and can be useful for the early identification of this harmful complication of liver cirrhosis.