losartan-potassium and Acute-On-Chronic-Liver-Failure

Advanced chronic liver disease is characterised by a long compensated phase followed by a rapidly progressive 'decompensated' phase, which is marked by the development of complications of portal hypertension and liver dysfunction. Advanced chronic liver disease is considered responsible for more than one million deaths annually worldwide. No treatment is available to specifically target fibrosis and cirrhosis; liver transplantation remains the only curative option. Researchers are investigating strategies to restore liver functionality to avoid or slow progression towards end-stage liver disease. Cytokine mobilisation of stem cells from the bone marrow to the liver could improve liver function. Granulocyte colony-stimulating factor (G-CSF) is a 175-amino-acid protein currently available for mobilisation of haematopoietic stem cells from the bone marrow. Multiple courses of G-CSF, with or without stem or progenitor cell or growth factors (erythropoietin or growth hormone) infusion, might be associated with accelerated hepatic regeneration, improved liver function, and survival.. To evaluate the benefits and harms of G-CSF with or without stem or progenitor cell or growth factors (erythropoietin or growth hormone) infusion, compared with no intervention or placebo in people with compensated or decompensated advanced chronic liver disease.. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and two trial registers (October 2022) together with reference-checking and web-searching to identify additional studies. We applied no restrictions on language and document type.. We only included randomised clinical trials comparing G-CSF, independent of the schedule of administration, as a single treatment or combined with stem or progenitor cell infusion, or with other medical co-interventions, with no intervention or placebo, in adults with chronic compensated or decompensated advanced chronic liver disease or acute-on-chronic liver failure. We included trials irrespective of publication type, publication status, outcomes reported, or language.. We followed standard Cochrane procedures. All-cause mortality, serious adverse events, and health-related quality of life were our primary outcomes, and liver disease-related morbidity, non-serious adverse events, and no improvement of liver function scores were our secondary outcomes. We undertook meta-analyses, based on intention-to-treat, and presented results using risk ratios (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CI) and I. We included 20 trials (1419 participants; sample size ranged from 28 to 259), which lasted between 11 and 57 months. Nineteen trials included only participants with decompensated cirrhosis; in one trial, 30% had compensated cirrhosis. The included trials were conducted in Asia (15), Europe (four), and the USA (one). Not all trials provided data for our outcomes. All trials reported data allowing intention-to-treat analyses. The experimental intervention consisted of G-CSF alone or G-CSF plus any of the following: growth hormone, erythropoietin, N-acetyl cysteine, infusion of CD133-positive haemopoietic stem cells, or infusion of autologous bone marrow mononuclear cells. The control group consisted of no intervention in 15 trials and placebo (normal saline) in five trials. Standard medical therapy (antivirals, alcohol abstinence, nutrition, diuretics, β-blockers, selective intestinal decontamination, pentoxifylline, prednisolone, and other supportive measures depending on the clinical status and requirement) was administered equally to the trial groups. Very low-certainty evidence suggested a decrease in mortality with G-CSF, administered alone or in combination with any of the above, versus placebo (RR 0.53, 95% CI 0.38 to 0.72; I. G-CSF, alone or in combination, seems to decrease mortality in people with decompensated advanced chronic liver disease of whatever aetiology and with or without acute-on-chronic liver failure, but the certainty of evidence is very low because of high risk of bias, inconsistency, and imprecision. The results of trials conducted in Asia and Europe were discrepant; this could not be explained by differences in participant selection, intervention, and outcome measurement. Data on serious adverse events and health-related quality of life were few and inconsistently reported. The evidence is also very uncertain regarding the occurrence of one or more liver disease-related complications. We lack high-quality, global randomised clinical trials assessing the effect of G-CSF on clinically relevant outcomes.

Topics: Acute-On-Chronic Liver Failure; Adult; Erythropoietin; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Granulocyte Colony-Stimulating Factor; Growth Hormone; Humans; Intercellular Signaling Peptides and Proteins; Liver Cirrhosis; Quality of Life; Stem Cells

Acute-on-chronic liver failure (ACLF) is characterized by a rapid progression to multiple organ failure and is associated with a very high mortality rate of 50-90%. Novel therapies are being investigated such as Erythropoietin (EPO). The aim of this prospective cohort study was to analyse the value of EPO in predicting prognosis and determine which patients may benefit most from EPO therapy.. According to the EASL-CLIF criteria, 104 consecutive patients were diagnosed with ACLF, and separated into two groups based on the type of insult: bleeding (Group A=31) or non-bleeding (Group B=73). In addition to a complete biochemical work-up and calculation of relevant prognostic scores, levels of EPO were measured on admission and correlated to the type of insult and final outcome.. Fifteen patients from Group A (mean age 60.32+/-9.29 years) had a lethal outcome and higher values of EPO on admission (319.26+/-326.58 mIU/ml) (p<0.005), compared to the 37 patients from Group B (mean age 59.9+/-10.19 years) with EPO levels at admission of 29.88+/-34.6 mIU/mL. In Group B, a cut-off EPO value of 30.65 mIU/mL had a sensitivity of 87.5% and a specificity 57.4% in predicting lethal outcome with an AUROC of 0.823. In Group A, a cut-off value of 229.95 mlU/mL had a sensitivity and specificity of 53.3% and 92.7%, respectively. The AUROC for this cut-off was 0.847.. Erythropoietin is superior to the standard prognostic scores in predicting 28-day mortality. Lower levels of EPO were detected in patients without bleeding as an insult indicating a possible therapeutic benefit in these patients.

Topics: Acute-On-Chronic Liver Failure; Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers; Erythropoietin; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Patient Admission; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors; ROC Curve; Time Factors