Infections in patients with cirrhosis are associated with high morbidity and mortality. Rifaximin is an antibiotic used to treat and prevent hepatic encephalopathy (HE); however, it has been ...suggested that it may play a crucial role in reducing infections in these populations.
To evaluate the role of rifaximin in preventing frequent cirrhosis-related infections spontaneous bacterial peritonitis, pneumonia, urinary tract infection (UTI), and bacteremia,
e infection, and all-cause mortality, as well as determining adverse effects and adherence to the drug.
A retrospective cohort study was conducted on decompensated cirrhotic patients with history of HE between January 2017 and November 2022 at a university center. Patients with cirrhosis, regardless of their etiology and severity, were included in the study, encompassing both hospitalized and outpatient cases. The statistical analysis included adjusted general linear models, Poisson regressions, and propensity score matching.
We included 153 patients. The mean age in the cohort was 60.2 ± 12.3 years and 67 (43.8%) were women. The main cause of cirrhosis was metabolic dysfunction-associated steatotic liver disease 52 (38%), and the median Model of End-Stage Liver Disease sodium was 16.5 (7-32). In the cohort, 65 (45%) patients used rifaximin. The mean follow-up was 32 months. Eighty-five patients with infectious events were recorded, and a total of 164 infectious events were registered. The main infectious events were UTIs (62, 37.8%) and pneumonia (38, 23.2%). The use of rifaximin was associated with lower infection rates, displaying an incidence rate ratio (IRR) of 0.64 95% confidence interval (CI) (0.47-0.89);
= 0.008. However, no discernible impact on mortality outcome was observed IRR 1.9, 95% CI (0.9-4.0);
= 0.09. There were no reported adverse effects, and no patient discontinued the therapy due to adverse effects.
The use of rifaximin significantly reduces infections in patients with cirrhosis and HE. Despite rifaximin was associated with a decreased all-cause mortality, this impact was not statistically significant in the adjusted analysis.
Alcohol consumption is among the five main factors responsible for the burden of disease and mortality. It is associated with changes in serum bile acids, and in recent years, extracellular vesicles ...(EV´s) and their Cargo have shown special interest in various lines of research due to their role in intercellular communication. This study aimed to characterize the serum levels of bile acids, changes in their composition, extracellular vesicles and their cargo in alcohol-associated liver disease (ALD).
Prospective cohort, years 2019-2021. They were divided into four groups; control group, alcohol-associated hepatitis (AH), alcohol-related cirrhosis, and alcohol use disorder (AUD). Measurement of serum bile acids and C4 was performed through Liquid Chromatography /Tandem Mass Spectrometry, serum measurement of FGF19 and the serum concentration of extracellular vesicles through NTA (nanoparticle tracking analysis) and their cargo of bile acids.
A greater concentration of total bile acids was measured in the AUD group (1366.28 ng/ml) compared to the control group (552.42 ng/ml) (p = 0.003). The concentration of chenodeoxycholic acid is higher in the group of patients with AH (734.23 ng/ml) (p=0.04). The EV´s concentration is higher in the HA groups (1.292 E^11 ± 6.4E^10 particles/ml) and in AUD (9.9E^10+ 4.9E^ particles/ml) (p=0.005). It was possible to analyze the Cargo of BA in exosomes with proportional differences between the groups.
Serum bile acids, both in concentration and composition, are modified in patients with AUD and HA, respectively; both present a higher concentration of exosomes, which could be a hepato-specific, dynamic and potentially prognostic biomarker in subjects with ALD.
there are different variables in patients with alcohol associated liver disease (ALD) and enlisted patients for liver transplant (LT), such as ethnicity, that determine health disparities in access, ...morbidity and mortality. This study aimed to assess and measure the impact of ethnicity in ALD and patients enlisted for LT.
we conducted a retrospective study using U.S databases, the National Health and Nutrition Examination Survey (NHANES) and the United Network for Organ Sharing (UNOS) from 2011 to 2018. We created a multivariate model analyzing the clinical characteristics of the interviewed patients for NHANES. Alcohol consumption and ethnicity were self-reported. We also created a competing risks model for time to LT in enlisted patients.
of the 39,156 interviewed patients, 17.1% identified as Hispanic. In this group, the prevalence of ALD was 9.0% and the average consumption of pure alcohol was 2.3 L/year. The multivariate-adjusted model showed that Hispanics were independently associated with a higher risk of ALD (OR 1.30; 95%CI: 1.05-1.60, p=0.018). Of the enlisted patients, 13.6% were Hispanic. White ethnicity, lower age, male sex, higher MELD score, renal failure, lower BMI, higher education and private insurance were associated with a higher rate of LT. Hispanics were independently associated with a lower LT (HR 0.80; 95%CI: 0.74-0.87, p<0.001).
ethnicity is an important factor in healthcare outcomes. This is a growing area of interest, and research should be carried out to better our understanding of the impact that these disparities have on patients. Studying ethnic minority groups is needed to enable researchers to face the challenges of reducing and ultimately eliminating health disparities.
Acute-on-chronic liver failure (ACLF) is a severe clinical entity with organ failures and high short-term mortality. To Date, few ACLF reports have been published in Latin America. This study aimed ...to characterize patients with ACLF, identifying triggers, organ failure, and survival at 30, 90, and 180 days compared to patients with decompensated cirrhosis without ACLF.
Retrospective study of decompensated cirrhotic patients hospitalized (between 2017-2019) in three centers in Chile. We evaluated transplant-free survival using Kaplan-Meier curves and Cox-regression.
398 patients were included, a median age of 65.3±11.7-year-old, 50.5% female, 91 (22.9%) presented ACLF (8% ACLF-1, 6.3% ACLF-2, 8.6% ACLF-3); 6.6% underwent liver transplantation. ACLF patients were younger (63.6 vs. 66.0 years; p=0.045), had higher MELD-Na scores (27 23-32 vs. 17 13-23; p<0.001) and higher APACHE II scores (20.5 16-25 vs. 14 10-15; p<0.001) at admission. The most common triggers in both groups were infections (42.4%), gastrointestinal bleeding (23.2%), and alcohol intake (31.3%). Among decompensating factors, acute kidney injury at admission was associated with higher mortality (HR 2.2, 95%CI: 1.4-3.4; p<0.001). The main organ failures were kidney (60.4%), circulatory (49.5%), and brain (48.4%). Organ failures were more frequent in ACLF-3, except renal failure (greater in ACLF-1). Transplant-free survival at 180 days was 73.7% in patients without ACLF and 40% in ACLF (p<0.001). In a Cox regression adjusted by age and sex, transplant-free survival was significantly lower in ACLF-3 compared to patients without ACLF (HR 3.7, 95%CI: 2.3-5.7;p<0.001).
ACLF is an entity of younger patients, with lower global and transplantation-free survival at 180 days and multiple organ failure compared to decompensated cirrhotics without ACLF.
Alcohol-related liver disease (ALD) encompasses a spectrum of diseases caused by excessive alcohol consumption. ALD includes hepatic steatosis, steatohepatitis, variable degrees of fibrosis, ...cirrhosis, and alcohol-associated hepatitis (AH), the latter being the most severe acute form of the disease. Severe AH is associated with high mortality (reaching up to 30%–50%) at 90 days. The cornerstone of ALD, and particularly AH, treatment continues to be abstinence, accompanied by support measures such as nutritional supplementation and management of alcohol withdrawal syndrome (AWS). In severe AH with model for end-stage liver disease (MELD) score ≥21, corticosteroids can be used, especially MELD score between 25 and 39, where the highest benefit is achieved. Other key aspects of treatment include the early identification of infections and their associated management and the proper identification of potential candidates for liver transplantation. The development of new therapies based on the pathophysiology and mechanisms of liver injury are underway. This includes the modulation and management of the innate immune response, gut dysbiosis, bacterial translocation, and bacteria-derived products from the intestine. These hold promise for the future of AH treatment.
In hepatorenal syndrome-acute kidney injury (HRS-AKI), accurate and early diagnosis is crucial. HRS is a severe condition seen in advanced cirrhosis, requiring prompt recognition and proper ...management to enhance patient outcomes. Diagnosis of HRS-AKI relies on serum creatinine elevations, similar to other AKI cases in cirrhosis. However, distinguishing HRS-AKI from other renal impairments in these patients can be challenging. Biomarkers and clinical criteria aid in diagnosis and guide treatment. The management of HRS-AKI initially involves improving the haemodynamic profile using albumin and vasoconstrictors like terlipressin, a synthetic vasopressin analogue. Despite some reports linking terlipressin to increased adverse events compared with norepinephrine, it remains the preferred choice in HRS-AKI and acute-on-chronic liver failure due to its faster, stronger response and improved survival. Additional therapies like midodrine (alpha-1 adrenergic agonist), octreotide (somatostatin analogue) and transjugular intrahepatic portosystemic shunt are proposed as adjuvant treatments for HRS-AKI, aiming to improve vasoconstriction and renal blood flow. However, these adjunctive therapies cannot replace the definitive treatment for HRS-AKI—liver transplantation (LT). In cases unresponsive to medical management, LT is the only option to restore liver function and improve renal outcomes. Current evidence favours combined liver and kidney transplantation (CLKT) in certain situations. This review aims to evaluate the present evidence and recommendations on AKI in patients with cirrhosis, the pathophysiology of HRS-AKI, different treatments and indications for LT and CLKT. Understanding the complexities of managing HRS-AKI is crucial for optimising patient care and achieving better outcomes in this challenging clinical setting.
The long-term impact of alcohol-related public health policies (PHP) on the burden of liver disease is unclear. This study aimed to assess the association between alcohol-related PHP and ...alcohol-related health consequences; 2. To develop an instrument to quantify the establishment of alcohol-related PHP in each country.
We performed an ecological multi-national study including 169 countries. We recorded socio-demographic data and the presence of alcohol-related PHP in each country from the WHO Global Information System of Alcohol and Health (GISAH) in 2010. Data on alcohol-related health consequences was collected from the Global Burden of Disease database (between 2010-2019). We classified the WHO categories into five domains to design an instrument with criteria for a low, moderate, and strong establishment of PHP. We estimated an incidence rate ratio (IRR) using multilevel generalized linear models with a Poisson family distribution. The models were adjusted by population size, age structure, and gross domestic product. We also estimated a preparedness index using multiple correspondence analysis.
The table summarizes the final instrument. We included 169 countries; the median preparedness index was 54 34.9-76.8. The preparedness index was associated with lower alcohol-associated liver disease (ALD) mortality (IRR:0.25, 95%CI: 0.06-1.09, p=0.064), cancer mortality (IRR:0.22, 95%CI: 0.05-0.97, p=0.046), hepatocellular carcinoma (HCC) mortality (IRR:0.20, 95%CI: 0.04-0.95, p=0.043), and cardiovascular mortality (IRR:0.15, 95%CI: 0.04-0.61, p=0.008). There was also a trend to lower alcohol use disorder prevalence (IRR:0.25, 95%CI: 0.06-1.09, p=0.064). The highest linear associations were observed in the Americas and Africa, while Europe exhibits a nonlinear association.
The preparedness index on alcohol policies is a valuable instrument to assess the establishment and strength of PHP. Those countries with a higher number of PHP had lower mortality due to ALD, cancer, HCC, and cardiovascular diseases. Our results strongly encourage the development and implementation of PHP on alcohol consumption worldwide.
Alcohol consumption represents a major factor of morbidity and mortality, with a wide range of adverse medical implications that practically affect every organ system. It is the fifth major cause of ...deaths in men and women and causes up to 139 million disability-adjusted life years. Solid evidence places the risk as undoubtedly correlated to the length of time and amount of alcohol consumption. While alcohol-related liver disease represents one of the most studied and well-known consequences of alcohol use, the term itself embodies a wide spectrum of progressive disease stages that are responsible for almost half of the liver-related mortality worldwide. We discuss the staged alcohol-related fatty liver, alcohol-related steatohepatitis and, finally, fibrosis and cirrhosis, which ultimately may end up in a hepatocellular carcinoma. Other comorbidities such as acute and chronic pancreatitis; central nervous system; cardiovascular, respiratory and endocrine system; renal disease; urological pathologies; type 2 diabetes mellitus and even infectious diseases are reviewed in their relation to alcohol consumption. This article reviews the impact of alcohol use on different systems and organs, summarizing available evidence regarding its medical implications. It examines current basic and clinical data regarding mechanisms to highlight factors and processes that may be targetable to improve patient outcomes. Although alcohol use is a part of many cultural and social practices, as healthcare providers we must identify populations at high risk of alcohol abuse, educate patients about the potential alcohol-related harm and provide appropriate treatment.
The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. The most common manifestations are mildly elevated alanine aminotransferase and aspartate ...aminotransferase, with a prevalence of 16-53% among patients. Cases with severe coronavirus disease 2019 (COVID-19) seem to have higher rates of acute liver dysfunction, and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization. Patients with chronic liver diseases also have a higher risk of severe disease and mortality (mainly seen in patients with metabolic-associated fatty liver disease). Several pathways of damage have been proposed in the liver involvement of COVID-19 patients; although, the end-cause is most likely multifactorial. Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection. This enzyme is expressed widely in cholangiocytes and less in hepatocytes. Other factors attributed to liver damage include drug-induced liver injury, uncontrolled release of proinflammatory molecules (“cytokine storm”), pneumonia-associated hypoxia, and direct damage by the infection. Hepatic steatosis, vascular thrombosis, fibrosis, and inflammatory features (including Kupffer cell hyperplasia) are the most common liver histopathological findings in deceased COVID-19 patients, suggesting important indirect mechanisms of liver damage. In this translational medicine-based narrative review, we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19, the histopathological findings, and the impact of these mechanisms in patients with chronic liver disease.
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