Effects of an Eight Week Very Low-Calorie Ketogenic Diet (VLCKD) on White Blood Cell and Platelet Counts in Relation to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Subjects with Overweight and Obesity.

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are frequently associated conditions characterized by low-grade inflammation. Very low-calorie ketogenic diet (VLCKD) strategies are commonly used to simultaneously obtain weight loss and an improvement of liver steatosis. We evaluated the efficacy of 8 weeks' VLCKD in decreasing the white blood cell (WBC) and platelet (PLT) counts, as well as liver steatosis and fibrosis, diagnosed using transient elastography (FibroScan). Metabolic and anthropometric parameters commonly associated with MASLD were also evaluated. This study included 87 participants; 58 women and 29 men aged between 18 and 64 years with overweight (18%) or obesity (82%), but not taking any medication. Anthropometric measurements, bioimpedance analysis, and biochemical assays were performed before and after the dietary intervention. BMI (kg/m2) (p-value < 0.001), waist circumference (cm) (p-value < 0.001), and fat mass (kg) (p-value < 0.001) were significantly decreased following VLCKD. After VLCKD, the FibroScan parameter CAP (db/m), which measures the accumulation of fatty liver, significantly decreased (p-value < 0.001), as did liver stiffness (kPA), the FibroScan parameter quantifying liver fibrosis (p-value < 0.05). Seemingly, WBC (p-value < 0.001) and PLT (p-value < 0.001) counts were lowered by VLCKD in the whole group; however, the decrease in WBC and platelet counts were significant only in patients with steatosis (CAP ≥ 215 dB/m). Fasting blood glucose (p-value < 0.001), insulin (p-value < 0.001), HbA1c (p-value < 0.001), triglycerides (p-value < 0.001), total cholesterol (p-value < 0.001), LDL-cholesterol (p-value < 0.001), HDL-cholesterol (p-value < 0.001); γGT (p-value < 0.001) blood levels and insulin resistance (as measured by HOMAIR) (p-value < 0.001); and systolic (p-value < 0.001), and diastolic (p-value < 0.001) blood pressure levels, were all significantly lower after VLCKD. In contrast, blood levels of vitamin D were higher following the diet (p-value < 0.001). We conclude that treating subjects with overweight and obesity with VLCKD is followed by a simultaneous reduction in WBCs and platelets, the expression of low-grade inflammation, and of liver steatosis and fibrosis. Therefore, we can hypothesize that VLCKD decreases general and liver low-grade inflammation, thus improving liver health.

Impact of Fresh Table Grape Intake on Circulating microRNAs Levels in Healthy Subjects: A Significant Modulation of Gastrointestinal Cancer-Related Pathways.

SCOPE: The study aims to investigate the effects of fresh table grape consumption in healthy subjects on circulating levels of the most common human microRNAs (miRNAs). The regulatory network governed by these modulated miRNAs is also investigated. METHODS AND RESULTS: Autumn Royal table grape, used in this study, is chosen for its high polyphenolic content and antioxidant properties. The study is a randomized controlled trial, in which 40 consecutive subjects are recruited on a voluntary basis and randomly assigned to two groups of the study, the control group, receiving only dietary recommendations and a grape group receiving a daily dose of 5 g of fresh table grape per kg of body weight for 21 days. All analyses are performed at baseline and after 21 days of dietary treatment. Circulating miRNAs levels are detected by Real-Time quantitative PCR (RT-qPCR) followed by bioinformatic functional analysis. The study identifies 20 circulating miRNAs differentially expressed in healthy subjects after grape intake, and in particular, 18 of 20 are down-regulated and 2 are up-regulated. CONCLUSION: The dietary intake of table grape affects circulating miRNAs levels in healthy subjects, particularly the miRNAs related to pathways involved in counteracting cancer development, including gastrointestinal cancers.

Genetic Associations of Alexithymia in Predicting Interferon-Induced Depression in Chronic Hepatitis C.

BACKGROUND: Previous studies have shown that alexithymia is associated with gene polymorphisms that regulate the availability of serotonin (5-HT) in the brain. Since the 5-HT network is involved in interferon (IFN)-induced depression, this paper aimed to investigate the role of alexithymia and the functional gene variants of the 5-HT1A receptor (HTR1A) and the 5-HT transporter (5-HTTLPR) in induction of depression during antiviral treatment. METHODS: The depressive symptoms of 130 consecutive patients with chronic hepatitis C and no current psychopathology were measured during treatment with IFN and ribavirin (6-12 months) and at a 6-month follow-up. At baseline, alexithymia and 2 genotypes (5-HTTLPR and HTR1A) were also assessed. RESULTS: Patients with homozygosity for HTR1A-G and 5-HTTLPR long alleles had significantly higher levels of alexithymia. After controlling for sociodemographic and disease-related factors, alexithymia and HTR1A-G polymorphism, both separately (20-22%) and jointly (14-16%), significantly and independently predicted the development of IFN-induced depression. CONCLUSIONS: Subjects carrying HTR1A-G and 5-HTTLRP double long alleles are more vulnerable to alexithymia. Also patients with a higher level of alexithymia and the HTR1A-G gene variant are more vulnerable to experiencing IFN-induced depressive symptoms. The clinical implications of targeting alexithymia and HTR1A receptors as a possible treatment option for mood disorders should be investigated in further studies.

Serotonin gene polymorphisms and lifetime mood disorders in predicting interferon-induced depression in chronic hepatitis C.

BACKGROUND: IFN-induced depression is a suitable model for investigating vulnerability to depression. We aimed at investigating the role of two vulnerability factors, lifetime mood disorder (LMD) and 5-HT-related gene polymorphisms in treated patients with infection by Hepatitis C Virus (HCV). METHODS: Depressive symptoms of 130 consecutive HCV patients with no current psychopathology were measured during treatment with interferon and ribavirin. At baseline, LMD and 3 genotypes (5-HTTLPR, HTR1A, and TPH2) were also assessed. RESULTS: Subgroups of 43 patients with LMD, 96 with HTR1A-G allele, and 12 with both LMD and HTR1A-G homozigosity scored significantly higher to depression compared to the remaining patients during antiviral therapy. At the multiple regression analysis, LMD and HTR1A-G, whether separately or combined together, explained a similar amount of 10-22% of depression score variance, after controlling for the associated variables (age and gender). LIMITATIONS: HCV patients referred to a tertiary care center are not representative of all patients with chronic hepatitis C. Mediating factors, including proinflammatory cytokines and other potentially relevant gene polymorphisms, could not be evaluated. Patients were not stratified by degree of liver inflammation. LMD diagnoses were not cross-checked with medical records and IFN-induced depression was measured with a self-report scale only. CONCLUSIONS: History of mood disorders and HTR1A G allele variation, the C-1019G polymorphism of the transcriptional control region of the 5-HT1A receptor, independently predicted the incidence of IFN-induced depression in HCV patients, whether separately or jointly considered and although not reciprocally associated.

The role of alexithymia in quality of life impairment in patients with chronic hepatitis C during antiviral treatment.

This study aimed to investigate the role of alexithymia in the quality of life of patients with chronic hepatitis C treated with antiviral therapy. A consecutive sample of 124 patients were evaluated at baseline, during, and 6months after treatment with interferon and ribavirin. At baseline past mood disorders and alexithymia and, at each index visit, adverse events, psychological distress, and disease-specific quality of life were assessed with validated instruments. Patients with past mood disorders and alexithymia had impaired levels of quality of life, psychological distress, and treatment-related adverse events. However, after controlling for covariates, poor quality of life was independently predicted by alexithymia and psychological distress before (R(2)=0.60) and 6months after (R(2)=0.69) the antiviral treatment while during treatment (at 3months and the end of therapy) by depression and somatic adverse events (R(2)=0.67 and 0.69, respectively). Alexithymia rather than history of mood disorders resulted to be an independent predictor of impaired quality of life not only before but also 6months after the end of treatment. Given the association with proneness to health-compromising behaviors, clinicians are encouraged to pay closer attention to long-term psychological and somatic effects of antiviral treatment in patients with alexithymic characteristics.

Epidemiology of HCV infection in the general population: a survey in a southern Italian town.

OBJECTIVES: The objective of this study was to estimate the seroprevalence of hepatitis C virus (HCV) in the general population older than 18 years of age in a southern Italian town. METHODS: The survey was conducted from July 2005 through January 2007 in Putignano, Bari, Apulia. A random 1:5 sampling from the list of records maintained by general practitioners was used. Serology for HCV, hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), and genotyping for HCV were performed. RESULTS: Of a total of 2,195 serum samples tested, 58 (2.6%) were positive for anti-HCV antibodies. The prevalence increased from 1% in subjects aged <30 years to 7.7% in those aged 70 years and was similar in both males and females (3.1 vs. 2.4%, P=0.4). Approximately one-third of 58 positive subjects also showed alanine transaminase levels and 53.5% tested positive for HCV RNA by TaqMan PCR. Genotypes 2a and 1b were represented in 21 and 10 subjects, respectively. In a multivariate logistic regression analysis, age (adjusted odds ratio (OR) 1.05; 95% confidence interval (CI): 1.03-1.07), blood transfusion (adjusted OR 3.3; 95% CI: 1.7-6.3), and household contact with HCV-infected individuals (adjusted OR 4.8; 95% CI: 1.8-13.1) were the independent variables predictive of HCV infection. The overall HBsAg and anti-HBc prevalence rates were 0.5 and 12%, respectively. CONCLUSIONS: This survey confirms that HCV infection is clearly also declining in southern Italy, especially among the elderly. HCV genotype 2a predominates, reflecting the current epidemiology of HCV in Italy. Age, blood transfusion, and household contact with HCV-infected individuals may have had a role in the spread of HCV infection.

Onset of type 1 diabetes mellitus during peginterferon alpha-2b plus ribavirin treatment for chronic hepatitis C.

A 61-year-old man was observed to develop type 1 diabetes mellitus following a 3-month treatment with recombinant alpha-2b peginterferon combined with ribavirin for chronic hepatitis C. Serum samples, collected before the start of therapy and 2 months after the diagnosis of diabetes mellitus, revealed islet-cell antibodies at a titer of 20 and 40 JDF-U, respectively, and glutamic acid decarboxylase autoantibodies at a value of 76.5 and 196 IU/ml, respectively. Antibodies to second islet autoantigen were persistently negative. HLA class II typing revealed the presence of DRB1*04/DRB1*14, DQA1*0303-0104 and DQB1*04-0503 alleles. Eight months after the onset of type 1 diabetes mellitus, the patient is still receiving 30 IU insulin daily; the liver function tests are normal and serum hepatitis C virus RNA is negative. These data confirm that, in patients with potential diabetes mellitus, the disease may become manifest as a side-effect during therapy with peginterferon-alpha plus ribavirin. The patient as a candidate for interferon treatment should therefore be investigated, in addition to thyroid autoimmunity, also for pancreatic autoantibodies before starting therapy.