Low-to-moderate alcohol consumption is associated with increased fibrosis in individuals with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: Both metabolic dysfunction and alcohol consumption cause steatotic liver disease (SLD). New nomenclature and distinction of metabolic dysfunction-associated SLD (MASLD) and MetALD categories is based on arbitrary thresholds of alcohol intake. We assessed the impact of different levels of alcohol consumption on SLD severity and its interaction with metabolic comorbidities. METHODS: Population-based study with transient elastography (FibroScan®) data from participants in Spain (derivation) and U.S. (validation) cohorts. Controlled attenuation parameter (CAP≥275 dB/m) identified SLD. At least one cardiometabolic risk factor was required to define MASLD. Among MASLD patients, low alcohol consumption was defined as an average of 5-9 drinks/week, moderate consumption as 10-13 drinks/week for females and 10-20 drinks/week for males, and increased alcohol intake (MetALD) as 14-35 drinks/week for females and 21-42 drinks/week for males. Significant fibrosis was defined as LSM≥8 kPa and at-risk MASH as FAST score≥0.35. RESULTS: The derivation cohort included 2,227 subjects with MASLD (9% reported low, 14% moderate alcohol consumption), and 76 cases with MetALD. Overall prevalence of significant fibrosis and at-risk MASH were 7.6% and 14.8%, respectively. In the multivariable analysis, alcohol consumption was independently associated with significant fibrosis and at-risk MASH. A dose-dependent increase in the prevalence of significant fibrosis and at-risk MASH was observed between the number of drinks/week and the number of cardiometabolic factors. The validation cohort included 1,732 participants with MASLD, of whom 17% had significant fibrosis and 13% at-risk MASH. This cohort validated the association between moderate intake and MASLD at risk of progression (OR=1.69 [95%CI 1.06-2.71]). CONCLUSIONS: Moderate alcohol intake is commonly seen in MASLD and increases the risk of advanced disease, in a similar magnitude to MetALD spectrum. IMPACT AND IMPLICATIONS: Metabolic risk factors such as overweight, diabetes or dyslipidemia, and alcohol consumption can cause liver disease. These factors frequently co-exist, but their joint effects on liver fibrosis remain uncertain. This study analyzes subjects form the general population with metabolic dysfunction-associated steatotic liver disease (MASLD) enrolled in Spain and U.S. We show that moderate alcohol consumption has a supra-additive effect with metabolic risk factors, exponentially increasing the risk of liver fibrosis. These results suggest that patients with unhealthy metabolic status and MASLD have no safe limits of daily alcohol intake.

Binge drinking at time of bariatric surgery is associated with liver disease, suicides, and increases long-term mortality.

BACKGROUND AND AIMS: Alcohol use disorder has been reported in patients undergoing bariatric procedures, but the pattern of alcohol consumption has not been evaluated. We investigated the prevalence, risk factors, and impact of binge drinking (BD) at the time of surgery and during follow-up. METHODS: A prospective, longitudinal study of subjects undergoing bariatric surgery was included in the LABS-2 registry between 2006 and 2009. Participants with AUDIT questionnaire at the time of surgery and a minimum of 12 months follow-up were included. BD was defined as consuming ≥5 drinks on at least 1 occasion in the previous month. Liver biopsies were obtained during bariatric procedures in not all cases. Survival analysis was performed with the adjusted Cox regression model and competing risk. RESULTS: A total of 2257 subjects were included, with a median follow-up of 79 months. The prevalence of BD at time of surgery was 12%, and it raised up to 23% during follow-up. Patients with BD predominantly had a binge eating disorder (OR=1.35 [95% CI: 1.04-1.76]), regularly consumed fast food [OR=1.4 (95% CI: 1.07-1.85)] and used other drugs (OR=2.65 [95% CI: 1.74-4.04]). Within liver biopsies evaluation, BD showed higher hepatic iron deposits (OR=3.00 [95% CI: 1.25-7.21]). BD at the time of surgery was associated with a higher risk of BD during follow-up (OR=10.49 [95% CI: 7.86-14.00]) and long-term mortality (HR: 3.21 [95% CI: 1.67-6.18]). Specific causes of death in these patients with BD were liver disease (p=0.020), suicide (p=0.015), neoplasms (p=0.034), and respiratory (p=0.025). CONCLUSIONS: The prevalence of BD in patients undergoing bariatric surgery is high and increases the risk of postoperative liver disease, suicides, and long-term mortality.

Liver disorders and celiac disease.

Celiac disease (CD) is a chronic autoimmune enteropathy triggered by gluten intake. Celiac hepatitis is the most common hepatic manifestation of CD, it usually responds to a gluten-free diet (GFD) and is sometimes the only manifestation in paucisymptomatic CD. Through this descriptive observational study, we determined the prevalence of liver abnormalities upon diagnosis of CD. A total of 140 patients were included. The prevalence of alterations in liver markers at diagnosis of CD was 47%. In 2.9% of patients, liver abnormalities were the only manifestation at diagnosis. A higher prevalence of liver alterations was found in those patients who presented a more severe histological alteration (MARSH 3c).

Prevalence and clinical impact of alcohol withdrawal syndrome in alcohol-associated hepatitis and the potential role of prophylaxis: a multinational, retrospective cohort study.

Background: The prevalence and impact of alcohol withdrawal syndrome (AWS) in patients with alcohol-associated hepatitis (AH) are unknown. In this study, we aimed to investigate the prevalence, predictors, management, and clinical impact of AWS in patients hospitalized with AH. Methods: A multinational, retrospective cohort study enrolling patients hospitalized with AH at 5 medical centres in Spain and in the USA was performed between January 1st, 2016 to January 31st, 2021. Data were retrospectively retrieved from electronic health records. Diagnosis of AWS was based on clinical criteria and use of sedatives to control AWS symptoms. The primary outcome was mortality. Multivariable models controlling for demographic variables and disease severity were performed to determine predictors of AWS (adjusted odds ratio [OR]) and the impact of AWS condition and management on clinical outcomes (adjusted hazard ratio [HR]). Findings: In total, 432 patients were included. The median MELD score at admission was 21.9 (18.3-27.3). The overall prevalence of AWS was 32%. Lower platelet levels (OR = 1.61, 95% CI 1.05-2.48) and previous history of AWS (OR = 2.09, 95% CI 1.31-3.33) were associated with a higher rate of incident AWS, whereas the use of prophylaxis decreased the risk (OR = 0.58, 95% CI 0.36-0.93). The use of intravenous benzodiazepines (HR = 2.18, 95% CI 1.02-4.64) and phenobarbital (HR = 2.99, 95% CI 1.07-8.37) for AWS treatment were independently associated with a higher mortality. The development of AWS increased the rate of infections (OR = 2.24, 95% CI 1.44-3.49), the need for mechanical ventilation (OR = 2.49, 95% CI 1.38-4.49), and ICU admission (OR = 1.96, 95% CI 1.19-3.23). Finally, AWS was associated with higher 28-day (HR = 2.31, 95% CI 1.40-3.82), 90-day (HR = 1.78, 95% CI 1.18-2.69), and 180-day mortality (HR = 1.54, 95% CI 1.06-2.24). Interpretation: AWS commonly occurs in patients hospitalized with AH and complicates the hospitalization course. Routine prophylaxis is associated with a lower prevalence of AWS. Prospective studies should determine diagnostic criteria and prophylaxis regimens for AWS management in patients with AH. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Subclinical versus advanced forms of alcohol-related liver disease: Need for early detection.

Alcohol-related liver disease (ALD) consists of a wide spectrum of clinical manifestations and pathological features, ranging from asymptomatic patients to decompensated cirrhosis and hepatocellular carcinoma. Patients with heavy alcohol intake and advanced fibrosis often develop a subacute form of liver failure called alcohol-induced hepatitis (AH). Globally, most patients with ALD are identified at late stages of the disease, limiting therapeutic interventions. Thus, there is a need for early detection of ALD patients, which is lacking in most countries. The identification of alcohol misuse is hampered by the existence of alcohol underreporting by many patients. There are useful biomarkers that can detect recent alcohol use. Moreover, there are several non-invasive techniques to assess the presence of advanced fibrosis among patients with alcohol misuse, which could identify patients at high risk of liver related events or early death. In this review, we discuss differences between early stages of ALD and AH as the cornerstone of advanced forms. A global overview of epidemiological, anthropometric, clinical, analytical, histological, and molecular differences is summarized in this article. We propose that campaigns aimed at identifying patients with subclinical forms can prevent the development of life-threatening forms.

Thiopurine adherence: a high prevalence with low impact on UC outcomes

Introduction: thiopurines are used as maintenance therapy in patients with ulcerative colitis (UC). There are contradictory results regarding the relationship between adherence to treatment and risk of relapse.Objectives: to quantify and evaluate the trends in thiopurine prescription rates, and to determine the impact and risk factors of non-adherence.Methods: analytical, observational, retrospective study of UC patients taking thiopurines included in the ENEIDA single-center registry from October 2017 to October 2019. Adult patients in clinical remission at the beginning of the study on thiopurines maintenance treatment for at least 6 months before recruitment were included. Adherence was evaluated with an electronic pharmaceutical prescription system. Adherence was considered when 80 % or more of the prescribed medication was dispensed at the pharmacy. Kaplan-Meier curves and a regression model were used to examine year-to-year treatment dispensation, and to identify factors associated with non-adherence.Results: a total of 41 patients were included, of whom 71 % were males with a mean age of 44 (14), and 26.8 % were concomitantly managed with biological therapy. Overall, 22 % were non-adherent to thiopurines. No predictive factors of non-adherence were identified. Adherence rate did not correlate with disease activity during two years of follow-up (OR 1.6; 95 % CI = 0.3-9.1). Left-sided colitis and concomitant biological treatment were related with disease relapse (p ≤ 0.01).Conclusion: adherence to thiopurines in UC patients is high (78 %). Non-adherence is not related to clinical or pharmacological factors. Adherence rate was not associated with disease activity. (AU)

Thiopurine adherence: a high prevalence with low impact on UC outcomes.

INTRODUCTION: thiopurines are used as maintenance therapy in patients with ulcerative colitis (UC). There are contradictory results regarding the relationship between adherence to treatment and risk of relapse. OBJECTIVES: to quantify and evaluate the trends in thiopurine prescription rates, and to determine the impact and risk factors of non-adherence. METHODS: analytical, observational, retrospective study of UC patients taking thiopurines included in the ENEIDA single-center registry from October 2017 to October 2019. Adult patients in clinical remission at the beginning of the study on thiopurines maintenance treatment for at least 6 months before recruitment were included. Adherence was evaluated with an electronic pharmaceutical prescription system. Adherence was considered when 80 % or more of the prescribed medication was dispensed at the pharmacy. Kaplan-Meier curves and a regression model were used to examine year-to-year treatment dispensation, and to identify factors associated with non-adherence. RESULTS: a total of 41 patients were included, of whom 71 % were males with a mean age of 44 (14), and 26.8 % were concomitantly managed with biological therapy. Overall, 22 % were non-adherent to thiopurines. No predictive factors of non-adherence were identified. Adherence rate did not correlate with disease activity during two years of follow-up (OR 1.6; 95 % CI = 0.3-9.1). Left-sided colitis and concomitant biological treatment were related with disease relapse (p ≤ 0.01). CONCLUSION: adherence to thiopurines in UC patients is high (78 %). Non-adherence is not related to clinical or pharmacological factors. Adherence rate was not associated with disease activity.