Evaluation of Cardiovascular Risk Factors after Hepatitis C Virus Eradication with Direct-Acting Antivirals in a Cohort of Treatment-Naïve Patients without History of Cardiovascular Disease

Background: Hepatitis C virus (HCV) produces changes at multiple levels in host metabolism, especially in lipid profile and cardio-metabolic risk. It is unclear how HCV eradication by direct-acting antivirals (DAAs) modifies those changes. Objective: To evaluate the impact of DAA treatment on different risk factors associated with cardiovascular disease. Methods: Prospective study with two-year follow-up. All patients treated with DAAs in the Liver Clinic of a tertiary hospital were included. Patients co-infected with HBV or HIV, with other causes of liver disease, on lipid-lowering treatment, pregnant, or with previous HCV treatment were excluded. The results were analyzed using linear mixed models. Results: 167 patients (53% female, 9.6% cirrhosis) were included. Low plasma lipid levels were observed before initiating HCV eradication. During the first year after treatment with DAA, we observed a sustained increase in cholesterol, triglycerides, HDL cholesterol (only in men), and LDL-cholesterol levels. An ameliorated glycemic control was also observed with a decrease in fasting insulin and reduced HOMA. Iron metabolism and coagulation function also improved with lower levels of serum ferritin and prothrombin activity; these biochemical changes resulted in a new diagnosis of hypercholesterolaemia in 17.4% of patients, requiring initiation of statins in 15%. Two non-fatal cardiovascular events were observed during the first 2 years of follow-up. Conclusions: DAA treatments returned plasma lipids to the normal range without increasing either the occurrence of cardiovascular events or the consumption of lipid-lowering medication beyond what is normal in a sex- and age-matched population

Randomized Clinical Trial: Effects of β-Hydroxy-βMethylbutyrate (HMB)-Enriched vs. HMB-Free Oral Nutritional Supplementation in Malnourished Cirrhotic Patients

β-Hydroxy-β-methylbutyrate (HMB) supplementation increases muscle and strength mass in some muscle-wasting disorders. Malnutrition and sarcopenia are often present in liver cirrhosis. We aimed to investigate the effects of oral HMB supplementation on changes in body composition and liver status in patients with cirrhosis and malnutrition. In a randomized, controlled, double-blind trial, 43 individuals were randomized to receive twice a day and for 12 weeks an oral nutritional supplement (ONS) enriched with 1.5 g of calcium HMB per bottle or another supplement with similar composition devoid of HMB. Inclusion criteria were liver cirrhosis with at least one previous decompensation and clinical malnutrition. Liver function, plasma biochemistry analyses, and physical condition assessment were carried out at baseline, then after six and 12 weeks of supplementation. A total of 34 patients completed the clinical trial. An improvement in liver function and an increase in fat mass index were observed in both groups. None of the two ONS changed the fat-free mass. However, we observed an upward trend in handgrip strength and a downward trend in minimal hepatic encephalopathy in the HMB group. At the end of the trial and regardless of the supplement administered, fat mass content increased with no change in fat-free mass, while liver function scores and nutritional analytic markers also improved

Amino Acid Profile in Malnourished Patients with Liver Cirrhosis and Its Modification with Oral Nutritional Supplements: Implications on Minimal Hepatic Encephalopathy

Low plasma levels of branched chain amino acids (BCAA) in liver cirrhosis are associated with hepatic encephalopathy (HE). We aimed to identify a metabolic signature of minimal hepatic encephalopathy (MHE) in malnourished cirrhotic patients and evaluate its modification with oral nutritional supplements (ONS) enriched with ß-Hydroxy-ß-methylbutyrate (HMB), a derivative of the BCAA leucine. Post hoc analysis was conducted on a double-blind placebo-controlled trial of 43 individuals with cirrhosis and malnutrition, who were randomized to receive, for 12 weeks, oral supplementation twice a day with either 220 mL of Ensure® Plus Advance (HMB group, n = 22) or with 220 mL of Ensure® Plus High Protein (HP group, n = 21). MHE evaluation was by psychometric hepatic encephalopathy score (PHES). Compared to the HP group, an HMB-specific treatment effect led to a larger increase in Val, Leu, Phe, Trp and BCAA fasting plasma levels. Both treatments increased Fischer’s ratio and urea without an increase in Gln or ammonia fasting plasma levels. MHE was associated with a reduced total plasma amino acid concentration, a reduced BCAA and Fischer´s ratio, and an increased Gln/Glu ratio. HMB-enriched ONS increased Fischer´s ratio without varying Gln or ammonia plasma levels in liver cirrhosis and malnutrition, a protective amino acid profile that can help prevent MHE

Isthmin-1 (ISM1), a novel adipokine that reflects abdominal adipose tissue distribution in individuals with obesity

Abstract Background The assessment of obesity-related health risks has traditionally relied on the Body Mass Index and waist circumference, but their limitations have propelled the need for a more comprehensive approach. The differentiation between visceral (VIS) and subcutaneous (SC) fat provides a finer-grained understanding of these risks, yet practical assessment methods are lacking. We hypothesized that combining the SC-VIS fat ratio with non-invasive biomarkers could create a valuable tool for obesity-related risk assessment. Methods and results A clinical study of 125 individuals with obesity revealed significant differences in abdominal fat distribution measured by CT-scan among genders and distinct models of obesity, including visceral, subcutaneous, and the SC/VIS ratio. Stratification based on these models highlighted various metabolic changes. The SC/VIS ratio emerged as an excellent metric to differentiate metabolic status. Gene expression analysis identified candidate biomarkers, with ISM1 showing promise. Subsequent validation demonstrated a correlation between ISM1 levels in SC and plasma, reinforcing its potential as a non-invasive biomarker for fat distribution. Serum adipokine levels also correlated with the SC/VIS ratio. The Receiver Operating Characteristic analysis revealed ISM1’s efficacy in discriminating individuals with favorable metabolic profiles based on adipose tissue distribution. Correlation analysis also suggested that ISM1 was involved in glucose regulation pathways. Conclusion The study’s results support the hypothesis that the SC-VIS fat ratio and its derived non-invasive biomarkers can comprehensively assess obesity-related health risks. ISM1 could predict abdominal fat partitioning and be a potential biomarker for evaluating obesity-related health risks

Newborn screening for homocystinurias: recent recommendations versus current practice

Purpose: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. Methods: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and decision limits were converted to multiples of the median (MoM) to allow comparison between centres. Results: NBS programmes, algorithms and decision limits varied considerably. Only nine centres used the recommended second-tier marker total homocysteine (tHcy). The median decision limits of all centres were ≥ 2.35 for high and ≤ 0.44 MoM for low methionine, ≥ 1.95 for high and ≤ 0.47 MoM for low methionine/phenylalanine, ≥ 2.54 for high propionylcarnitine and ≥ 2.78 MoM for propionylcarnitine/acetylcarnitine. These decision limits alone had a 100%, 100%, 86% and 84% sensitivity for the detection of CBSD, MATI/IIID, iRMD and cRMD, respectively, but failed to detect six individuals with cRMD. To enhance sensitivity and decrease second-tier testing costs, we further adapted these decision limits using the data of 15 000 healthy newborns. Conclusions: Due to the favorable outcome of early treated patients, NBS for homocystinurias is recommended. To improve NBS, decision limits should be revised considering the population median. Relevant markers should be combined; use of the postanalytical tools offered by the CLIR project (Collaborative Laboratory Integrated Reports, which considers, for example, birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.Funding information: Mayo Clinic; Charles University; Ministry of Health of the Czech Republic Communicated by: Piero Rinaldoinfo:eu-repo/semantics/publishedVersio