Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, with a prevalence of 25–30%. Since its first description in 1980, NAFLD has been conceived as a ...different entity from alcohol-related fatty liver disease (ALD), despite that, both diseases have an overlap in the pathophysiology, share genetic–epigenetic factors, and frequently coexist. Both entities are characterized by a broad spectrum of histological features ranging from isolated steatosis to steatohepatitis and cirrhosis. Distinction between NAFLD and ALD is based on the amount of consumed alcohol, which has been arbitrarily established. In this context, a proposal of positive criteria for NAFLD diagnosis not considering exclusion of alcohol consumption as a prerequisite criterion for diagnosis had emerged, recognizing the possibility of a dual etiology of fatty liver in some individuals. The impact of moderate alcohol use on the severity of NAFLD is ill-defined. Some studies suggest protective effects in moderate doses, but current evidence shows that there is no safe threshold for alcohol consumption for NAFLD. In fact, given the synergistic effect between alcohol consumption, obesity, and metabolic dysfunction, it is likely that alcohol use serves as a significant risk factor for the progression of liver disease in NAFLD and metabolic syndrome. This also affects the incidence of hepatocellular carcinoma. In this review, we summarize the overlapping pathophysiology of NAFLD and ALD, the current data on alcohol consumption in patients with NAFLD, and the effects of metabolic dysfunction and overweight in ALD.
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 serious clinical entity, with no previous reports in Chile.
To characterize patients with ACLF in a Chilean University Hospital, identifying triggers, organ ...failure and survival at 30, 90, 180 days, compared to patients with decompensated cirrhosis without ACLF.
Retrospective cohort study of decompensated cirrhotic patients hospitalized in a chilean University Hospital between 2017-2019.
334 patients were included, 73 (22%) presented ACLF (33% ACLF-1, 30% ACLF-2, 37% ACLF-3); 16.4% underwent liver transplantation. Patients with ACLF were younger, and had higher MELD-Na and APACHE II on admission. The most common triggers in both groups were infections (42.4%), gastrointestinal bleeding (23.2%) and alcohol intake (31.3%). The main organ failures were kidney (60.2%) and brain (49.3%). All organ failures were more frequent in ACLF-3, except renal failure (greater in ACLF-1). Survival at 180 days was 74% in patients without ACLF and 58.3% in ACLF (p=0.004). Mortality was significantly higher in ACLF-2 and ACLF-3, when compared with patients without ACLF (HR 2.3 and 2.99, respectively; p<0.05). Transplant-free survival in cirrhotics without ACLF was 72.5% versus 43.1% with ACLF (p<0.001). The risk of mortality or transplantation was higher in ACLF-2 and ACLF-3, in contrast to patients without ACLF (HR 2.19 and 4.61, respectively; p <0.05).
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.
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.
It has been observed people with low-income-level (<IL) have greater liver injury due to alcohol consumption (AC), even when their consumption levels are lower or equal to those with ...high-income-level (>IL). The aim of this study was to evaluate alcohol-associated liver disease (ALD) paradox in Chile.
With data from the ENS 2016-17 (N=2,190; age 25-64) we constructed a logit regression model that estimated the effect hazardous AC (AUDIT≥8) on the probability of presenting ALD (GPT≥40 U/L). We focus on the interaction between hazardous AC and IL, controlling for the presence of metabolic syndrome (MS), diabetes mellitus (T2DM), obesity and tobacco.
The average AC was 39g of alcohol per week (13g women <IL; 23g women >IL; 64g men, without differences by IL). In women, hazardous AC only increased ALD among those >IL who presented with obesity or MS in combination with T2DM (+36% obesity+MS+T2DM; p<0.01). In men, hazardous AC only increased ALD among those with <IL (16% without comorbidities, 17% with tobacco, 22% with MS, 26% with obesity, and 28% with all; p<0.05).
ALD paradox can be observed in Chile among men, but not among women. The evaluated associated comorbidities increased the effect of hazardous AC on ALD. It is necessary to investigate how the IL determines the patterns of AC and comorbidities. Among men, <IL is likely to be associated with more harmful drinking patterns and a greater presence of comorbidities. Among women, >IL is likely associated with higher AC and more harmful consumption patterns.
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.
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